Komplikasi dan Luaran

Fatal Penyakit Campak

Yulia Iriani
UKK Infeksi dan Penyakit Tropis Ikatan Dokter Anak Indonesia
Divisi Infeksi dan Penyakit Tropis KSM Kesehatan Anak RSUP dr. Mohammad Hoesin/
Bagian Ilmu Kesehata Anak FK UNSRI Palembang

estimated 23.2 million deaths worldwide (Fig. 227.2)43
Measles eradication is biologically and technically feasible, and nations
in every WHO region have achieved elimination.73,86 In 2016 measles
elimination was verified in the WHO Region of the Americas (AMR).
The WHO Global Vaccine Action Plan endorsed by the World Health
Assembly in 2012 established measles elimination targets in five of the six
WHO regions by 2020. However, elimination progress has stalled due to
a massive global resurgence of measles in 2018 and 2019.7,73,87
In 2018 measles case counts increased by 167% compared with 2016.43
An increase in the incidence of measles was reported in five WHO regions
during 2016–2018 (Fig. 227.3).43 In 2018 the incidence of measles was
>600 per million in 5 (3%) of 179 reporting countries (Democratic Repub-
lic of the Congo [DRC], Liberia, Madagascar, Somalia, and Ukraine) and
accounted for 45% (157,239 cases) of all reported cases worldwide.43 In
2019–2020, the DRC experienced the world’s largest measles outbreak,
resulting in the deaths of >7000 children.88 In Samoa, the measles out-
tional travel with subsequent community spread.
The global resurgence of measles varies from country to country and
is caused by many factors, including weak or conflict-affected health
systems, inadequate surveillance of immunization campaigns, financial
barriers, inadequate country ownership, and increasing vaccine hesi-
tancy.7,43,73,88,89 In 2018 global coverage for one dose of MCV was 86%,
while coverage for 2 doses of MCV was only 69%.43 In post-elimination
countries, waning immunity may also be responsible for measles out-
breaks involving adults who had previously received 2 doses of MCV
and were protected during prior outbreaks.92 Vaccine-derived immunity
may wane over a decade due to absence of boosting by regular wild-type
MV following interruption of endemic circulation.73 The role of wan-
ing immunity in the changing epidemiology of measles needs further
investigation.
To achieve measles elimination goals, financial investments and politi-
cal will are needed to strengthen routine immunization systems, increase
2-dose MCV coverage and supplemental immunization activities,

Campak = Measles = Rubeola

break was associated with a population attack rate of approximately 3%.73
Major outbreaks in Venezuela (2018) and Brazil (2019) have resulted in
reestablishment of endemic measles transmission in the AMR region.43
Large measles outbreaks occurred in the European Union in 2017–2019
primarily due to immunity gaps and consequences of undervaccination
in most countries.89 In 2018 transmission was reestablished in countries
close immunity gaps, and improve case-based surveillance.43,73,93 Inno-
vative, affordable point-of-care measles diagnostic tests and alternative
vaccine delivery strategies, including microneedle patches, are being
developed for low-income countries.94–96 The microneedle patches could
be administered in low-income countries by community-based health-
care workers with minimal training.96!

• Penyakit virus yang sangat menular, distribusi global, 2.5

menyerang semua usia

2.0
• Kekebalan – imunisasi & infeksi alamiah

No. of measles deaths (millions)

• Menyebabkan komplikasi yang berpotensi parah pada 1.5
sekitar 30% -40% kasus dan kematian pada 1-2 per
seribu kasus.
1.0

• Masih sering ditemukan dan sering fatal di negara

berkembang 0.5

• Komplikasi relatif sering terjadi dan behubungan

dengan morbiditas dan mortalitas yang 0.0
signifikan. 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
Year

• Komplikasi dan kematian karena campak terjadi Estimated measles deaths in absence of vaccination
Estimated measles deaths with vaccination
lebih sering pada anak-anak muda, malnutrisi FIGURE 227.2.

atau defisiensi imun di daerah berkembang.

MMWR Morb Mortal Wkly Rep. 2019;68:1105-1111. https://pubmed.ncbi.nlm.nih.gov/31805033/.)

1195
Campak

• Penyebab: • Variasi manifestasi klinis:

• virus morbilli gol. paramyxoviridae • Classic/typical measles – imunokompeten
• Reservoir: • Atypical measles – telah mendapat killed vaccine
• manusia • Modified measles – partially immune person

• Transmisi: • Unsuall manifestation dan komplikasi

• unusuall manifestation – akibat langsung
• kontak langsung droplet respirasi
infeksi virus primer
• airborne
• komplikasi – kerusakan akibat infeksi sekunder
• Masa penularan: oleh MO lain
• 4 hari sebelum sd 4 hari setelah onset ruam
 a MeV are co-cultur
Myeloid tissue
Lymphoid tissue
replication undergo apo
Epithelium
MeV infe
of lymphocy
b Clinical signs lymphocytes
Prodromal phase with MeV pr
Fever by mitogens8
Rash contact of lym
Transmission F protein on
Immune suppression pendently of
0 7 14 21 28
H protein int
Time following MeV infection (days) Although
suppression
c d e MeV that res

Patogenesis apparent con

dox’ and mi
and depletio
cess referred
immune sup
to opportuni
to months af
population-l
delayed mor

Genetic and
Although Me
Figure 6 | Pathogenesis of measles. A schematic representation of the| kinetics
Nature Reviews DiseaseofPrimers and antigenic
a b). type viruses
c d). Koplik genome of M
e d courtesy insertions an
Measles Paul A Rota et al. variations ha
one of 24 ge
different wi
Both MeV-infected and uninfected lymphocytes from based on the
patients with measles are vulnerable to cell death69. MeV proteins (esp
infection of cultured human T cells revealed that con- assays with p
 F protein
H protein

Manifestasi Klinis
C Disease course D Com

Stadium Stadium Fever

Temperature (°C)
40
Masa inkubasi Stadium erupsi Ne
prodromal penyembuhan 39
ADEM,
38
• 10-21 hari • 3-5 hari (rentang • demam tinggi, • Ruam menjadi 37 O
1-7 hari) menetap setelah kecoklatan dan
• demam, malaise, ruam timbul (2-3 kemudian
„3C“ cough, hari) mengelupas Rash
coryza, • Ruam setelah 2-3 hari P
conjungtivitis, makulopapular • Batuk dapat
Koplik spots eritematosa menetal 10 hari Koplik’s spots
MEASLES 415
MEASLES 419
(berlangsung 5-6 atau lebih
hari), blanching • Demam menetap Adverse
Conjunctivitis
à non blanching, à infeksi
penyebaran sekunder
centrifugal:
ial measles outbreak in Taiwan 71
preaurikular ke Coryza
muka ke seluruh
A B
Image 84.4 Image 84.17
This unvaccinated 11-month-old acquired measles while traveling to the Philippines to
tubuh, konfluens
measles rash over Koplik spots of measles in a 7-year-oldvisit
boy.
pada badan dan
relatives. Note the bilateral conjunctivitis, crusting rhinorrhea, and morbilliform rash;
he also had a prominent staccato cough. Courtesy of Carol J. Baker, MD.
Courtesy of Larry Frenkel, MD.

diskret di bagian Cough

bawah;
1 2 3 4 5 6 7 8 9 10
• Anoreksia,
limfadenopati Incubation Prodromal Rash phase Convalescent
generalisata phase phase phase

Image 84.6 Figure 4: Measles epidemiology (A), transmission (B),disease course (C), and complications (D)
s displaying the This child with measles is showing the char-
y pattern on his acteristic red, blotchy rash on his buttocks Part A adapted from Fine PE and Clarkson JA.26 ADEM=acute demyelinating encephalomyelitis. MIBE=m
e third day of the and back during the third day of the rash.
s for Disease Measles is an acute, highly communicable
C D panencephalitis.
viral disease with prodromal fever, conjunc-
tivitis, coryza, cough, and Koplik spots on
the buccal mucosa. A red, blotchy rash 5
appears around day 3 of the illness, first on
the face and then becoming generalized.
Courtesy of Centers for Disease Control
cells, and nectin-4, a component of epithelial cell
36
membrane,
and Prevention.
adherens junctions.37 The distribution of these receptors into the cell
determines the broad cell types and tissues infected with Measles v
measles virus. The lifelong immunity that follows sequencing
measles is due to neutralising IgG antibodies to the variable reg
Prognosis

Pasien sehat Pasien immunocompromised

• Perjalanan penyakit biasanya tanpa komplikasi, • Campak berat dapat terjadi pada pasien dengan
berlangsung 7-10 hari dan pemulihan lancar imunitas seluler terganggu (misalnya, pasca
dengan terapi suportif adekuat transplantasi, pascakemoterapi, AIDS, defisiensi
imun bawaan)
• Perspektif global: campak merupakan salah satu
penyakit infeksi paling berat yang didapat pada • Tingkat kematian sangat tinggi (40%-70%)
masa kanak-kanak
• 1 dari penyebab kematian paling sering pada anak-
anak yang tidak diimunisasi di seluruh dunia
• Kematian terjadi karena pneumonia, ensefalitis,
atau dehidrasi
• Sebagian besar kematian akibat campak
terjadi pada anak-anak di bawah 5 tahun
Komplikasi
• Satu atau lebih komplikasi campak terjadi pada
sekitar 30% kasus
• Risiko komplikasi meningkat di daerah dengan sumber daya
terbatas, dengan CFR 4-10%
• Sering; diare, lainnya: otitis media,
bronkopneumonia, LTB
• Otitis media: 5-10% kasus, individu muda >>
• Dapat menyebabkan penyakit serius yang
memerlukan perawatan di RS (juga pada anak
sehat):
• 1 dari 1000 kasus: ensefalitis akut à kerusakan otak
permanen
• Sebagian besar kematian karena komplikasi saluran
napas atau ensefalitis (1-3 per 1000 kasus)
• SSPE: penyakit degeneratif jarang tetapi fatal, 7-10
tahun setelah infeksi campak
• Komplikasi dapat langsung karena virus rubeola,
atau sekunder karena superinfeksi bakteri atau
virus, atau karena mekanisme lain.
• Pasien risiko tinggi komplikasi:
• Anak < 5 tahun
• Dewasa > 20 tahun
• Wanita hamil
• Risiko luaran kehamilan buruk (mis. prematur,
abortus spontan) tinggi
• Risiko komplikasi lain (pneumonia, kematian)
tinggi
• Pasien imunokompromais (mis. HIV, leukemia, gizi
buruk)
 Komplikasi

Measles: complication; Jason An

https://calgaryguide.ucalgary.ca/?s=measles
 Measles can have regular temporal patterns, driven by
the accumulation and decline of susceptible individuals,
and cluster spatially among susceptible populations

Komplikasi
1964 1966 1968 1970 1972 1974 1976 1978
Saluran napas Neurologi Lain-lain:
Measles virus spreads first
• Otitis media to local lymphoid tissue
• Primary measles encephalitis • Gastrointestinal
• tersering: 7-9% and is then disseminated • jarang: 1-3/1000 kasus • diare (8%),
throughout the blood
• Pneumonia stream through infected • demam, sakit kepala, kejang dan perubahan status mental • gingivostomatitis, gastroenteritis,
• viral atau bakteriallymphocytes, infecting cells • mortalitas 10-15%, 25% survivors: sekuele hepatitis, mesenteric
in almost all organ systems
• 1-6%, tersering pada anak kecil, • RNA virus pada LCS lymphadenitis, dan appendicitis
immunocompromised, bumilperiod for
The incubation • Acute post measles encephalitis • Keratokonjungtivitis
measles is 12·5 days on
• penyebab terseringaverage
kematian • pada stadium konvalesens, khas: gangguan penglihatan, kesulitan berkemih, hiporefleksi • berat pada gangguan gizi,
(95% CI 11·8–13·2
(60%) days), with a range up to • beberapa merekomendasikan terapi steroid kebutaan
• Croup dan bronkiolitis23 days • Infeksi rekuren
• mortalitas 5% pada anak
• karena virus rubeola langsung • sangat jarang
• Measles inculsion body encephalitis
• Imun supresi
• tu pada anak imunodefisiensi, 1 tahun pasca infeksi
D Complications
• Perubahan status mental, defisit motorik fokal, kejang • supresi fungsi imun seluler

Neurological: • LCS: Ab measles, biopsi otak: RNA virus

Keratoconjunctivitis
ADEM, MIBE, SSPE
(blindness) • Subacute sclerosing panencephalitis (SSPE)
Otitis media
Stomatitis • penyakit neurologi degeneratif kronis, fatal
Laryngitis (croup)
• perubahan perilaku dan penurunan fungsi kognitif progresif lambat, perburukan fs
Pneumonia motorik & kejang
• 4 stadium
• I: gejala neurologis: perubahan kepribadian, letargi, kesulitan di sekolah, perilaku aneh
Adverse pregnancy – minggu-tahun
outcomes Diarrhoea • II: myoclonic jerk, dementia memberat, gangguan sensori dan motorik – 3-12 bulan
• III & IV: perburukan neurologis, flasiditas atau rigiditas dekortikasi, tanda & gejala
disfungsi autonom. Stad IV: keadaan vegetatif.
Death
• 7-10 tahun pasca infeksi primer WT virus
• 1/25.000 kasus, terutama infeksi pada usia <2 tahun
• Ab virus pada LCS
valescent
phase

d complications (D)
ephalomyelitis. MIBE=measles inclusion body encephalitis. SSPE=subacute sclerosing

ell membrane, enabling entry of viral ribonucleoproteins

rs into the cell cytoplasm.39
th Measles virus can be genetically characterised by
 • Infeksi Campak menekan sistem kekebalan tubuh,
menghapus memori imun tubuh (immune amnesia) à
rentan terhadap infeksi oportunistik untuk beberapa
minggu sampai beberapa bulan setelah infeksi.
• Campak berhubungan dengan supresi imun sementara
tetapi berat
• Infeksi virus campak mengurangi Ab yang sudah ada

Supresi Imun sebelumnya yang memberikan proteksi terhadap patogen lain

• In vivo
• supresi respons Mantoux
• limfopenia
• menggangu respons vaksinasi
• In vitro
• penurunan respons limfoproliferatif
• mengubah profil respons sitokin
• gangguan fungsi APC

Measles pathogenesis de Vries et al.

Tatalaksana
• Suportif:
• antipiretik (hindari penggunaan aspirin), cairan,
pengobatan superinfeksi sekunder, tatalaksana
komplikasi lain: kejang, gagal napas
• Vitamin A –
• menurunkan severity dan risiko komplikasi
• pada kasus berat
• dosis: (2 hari)
• Bayi <6 bulan − 50.000 IU
• 6 - 11 bulan − 100.000 IU
• ≥12 bulan − 200.000 IU units
• anak defisiensi vit A berat (seroftalmia, keratitis,
keratokonjungtivitis, ulkus kornea, bercak Bitot) –
tambahan dosis ketiga 4 minggu setelah dosis kedua
• Ribavirin (pendapat ahli):
• pada kasus berat, primary viral pneumonia
• pneumonia <1 tahun
• pneumonia > 1 tahun perlu dukungan ventilasi
• pasien supresi imun
• durasi ? – 5-7 hari, panduan klinis dan radiologis
• Tahap penelitian: terapi SSPE
• Isoprinosine – probabilitas survival >
• dosis 100 mg/kg/hari, dibagi 3 dosis
• dosis maksimal 3000 gm/hari
• IFN-alpha (iv atau intrathecal)
• Pencegahan pasca pajanan
 Red_Book_2020_SECTION 3_187-862.indd 507
Pencegahan Table 3.31. Post-exposure Prophylaxis (PEP) for Measles Exposures Who Are NOT

pasca Pregnant or Immunocompromised

Pajanan
PEP Type Depending on Time After Initial Exposure
Age Range Measles Immune Status a ≤3 days (≤72 hours) 4–6 days >6 days
All ages Immune • PEP not indicated. Exposed person has documented immunity.
(IgG positive, 2 MMR vaccine
doses, or born before 1957b)
<6 months Non-immune • Give intramuscular immunoglobulin (IMIG).c,d • PEP not indicated (too late).f
(due to age) • Home quarantinee for 28 days after last exposure. • Home quarantinee for 21 days
after last exposure.
Red_Book_2020_SECTION 3_187-862.indd 508

6–11 Non-immune • Give MMR vaccine (MMR • Give intramuscular • PEP not indicated (too late).f
c,d
months (due to age) vaccine preferred over IG). immunoglobulin (IMIG). • Home quarantinee for 21 days
Table 3.31. Post-exposure Prophylaxis (PEP) needed.
for Measles• Exposures Who forAre NOT after last exposure.

MEASLES
508
e
• No quarantine Home quarantine 28 days
Pregnant or Immunocompromised, continued
after last exposure.
Non-immune PEP Type
• Give MMR Depending on Time
vaccine. Afternot
• PEP Initial Exposure
indicated (too late).f
Age Range
months Measles Immune
(0 doses MMRStatus
a
vaccine or ≤3 days
IgG (≤72quarantine
• No hours) needed.b 4–6 days
• Home quarantinee for>621daysdays after last exposure, then give MMR
Adults negative)
Unknown measles immune • Give MMR vaccine. vaccine to protect from future exposures.
status • No quarantine needed.b • Obtain IgG titers to determine immunity. Home quarantinee while
1 dose of MMR vaccineb • Give 2nd MMR vaccine
awaitingdose
results; if IgG negative, quarantine for 21 days after last
months PEP).f IgG titers to determine immunity. Home quarantinee while
exposure (too late•forObtain
live vaccine. Not awaiting results; if IgG negative, quarantine for 21 days after last
• No quarantine needed.
Does contact work in exposure
setting with (too for PEP).f or
late(daycare/school)
children
healthcare facility
• Yes: Obtain titers Not
to determine immunity. Home quarantinee while
awaiting results; if• IgG
Agenegative,
1–3 years: Less for
quarantine likely to get
21 days sick
after lastbecause has 1 dose of MMR.

MEASLES
exposure (too late•for PEP).f
• No: Contact can reach out to their own provider to obtain measles
IgG titers.f
and give 2nd MMR to protect from future exposures.
Reproduced with permission from New York City Department of Health: https://www1.nyc.gov/assets/doh/downloads/pdf/imm/pep-measles-providers.pdf
a
30/03/21 1:10 PM

507
b

measles IgG titers or 2 MMR doses, consider them to have unknown immunity. Furlough non-immune healthcare workers for 21 days even if they get MMR PEP.
c
For patients who receive IG, provide these instructions: www1.nyc.gov/assets/doh/downloads/pdf/imm/stay-home-non-cases.pdf.
d
Dosing of intramuscular IG for infants aged <12 months is 0.5 mL/kg of body weight (max dose 15 mL). Administration of MMR or varicella vaccines must be delayed by 6 months after administra-
tion of intramuscular IG and by 8 months after intravenous IG.
e
When instructing home quarantine, ensure that all household members of the exposed individual are immune to measles. IG prolongs the incubation period to 28 days.
f
For patients who do not receive PEP, provide these instructions: www1.nyc.gov/assets/doh/downloads/pdf/imm/stay-home-cases.pdf.
30/03/21 1:10 PM
Pencegahan pasca Pajanan

Table 3.32. Post-exposure Prophylaxis (PEP) for Measles Exposures Who ARE Pregnant or
Immunocompromised

Measles Immune PEP Type Depending on Time After Initial Exposure

Category Age Range Statusa ≤3 days (≤72 hours) 4–6 days >6 days
Severely Immuno- <12 months Will need IG regardless of • Give intramuscular immunoglobulin (IMIG)c,d • PEP not indicated (too late)f
compromisedb measles immune status • Home quarantinee for 28 days after last exposure • Home quarantinee for
21 days after last exposure
• Give intravenous immunoglobulin (IVIG)c,d
• Home quarantinee for 28 days after last exposure
Pregnant n/a Immune
(IgG positive or 2 MMR • PEP not indicatedf
vaccine doses)
Non-immune • Give intravenous immunoglobulin (IVIG)c,d • PEP not indicated (too late)f

MEASLES
(IgG negative) • Home quarantinee for 28 days after last exposure • Home quarantinee for 21
days after last exposure

Unknown immunity • Draw titers (measles IgG) STAT to determine • PEP not indicated (too late)f
immunity; proceed as above based on titer results • Home quarantinee for
21 days after last exposure
Reproduced with permission from New York City Department of Health: https://www1.nyc.gov/assets/doh/downloads/pdf/imm/pep-measles-providers.pdf
a
b
Management of immunocompromised persons can be challenging and may require individualized decisions with provider based on immunocompromising condition or medications.

50
 Pencegahan pasca Pajanan

Table 3.32. Post-exposure Prophylaxis (PEP) for Measles Exposures Who ARE Pregnant or

510
Immunocompromised, continued

Severely immunocompromising conditions (per ACIP and IDSA)* include:

•
•
•
• On cancer chemotherapy**
• Post solid organ transplantation**
•
• **

• After hematopoietic stem cell transplant, duration of high-level immunosuppression is highly variable and depends on type of transplant (longer for allogenic than autologous), type of donor and
stem cell source, and post-transplant complications such as graft-versus-host disease and their treatments**
• 3
(age >5 years).
Low-level immunosuppression: In the absence of published guidance on exposed persons with low-level immunosuppression, consider assessing presumptive immunity to measles (measles IgG
positive or 2 MMR vaccine doses) to determine if PEP is indicated. If not immune to measles, give PEP as MMR (if not contraindicated and within 72 hours of initial exposure). Consider intravenous
IGc if MMR is contraindicated or if it is too late for MMR (day 4–6 after initial exposure) with home quarantine for 28 days after last exposure. If no PEP is given because it is too late, home quaran-
tine for 21 days after last exposure.e

MEASLES
c
For patients who receive IG, provide these instructions: www1.nyc.gov/assets/doh/downloads/pdf/imm/stay-home-non-cases.pdf.
d
Dosing of intramuscular IG for infants aged <12 months: 0.5 mL/kg of body weight (max dose 15mL). Dosing of intravenous IG for pregnant women not immune to measles and immunocompro-
mised persons: 400 mg/kg. MMR or varicella vaccine administration must be delayed by 6 months and 8 months after intramuscular and intravenous IG, respectively.
e
When implementing home quarantine, ensure that all household members of the exposed individual are immune to measles. IG prolongs the incubation period to 28 days.
f
For patients who do not receive PEP, provide these instructions: www1.nyc.gov/assets/doh/downloads/pdf/imm/stay-home-cases.pdf.
*
References: Centers for Disease Control and Prevention. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013. MMWR Recomm Rep. 2013:62(RR-4):1-34; and Rubin LG,
Levin MJ, Ljungman P, et al. 2013 IDSA Clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58(3):e44-e100
**
Check guidance/discuss with treating provider as duration of immunosuppression during or following chemotherapy, transplants, or biologic immune modulators may vary.
Terima kasih