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MANIFESTASI KLINIS MALARIA RINGAN
( Tanpa Komplikasi )
R I S N A
Div. Penyakit Tropik & Infeksi, Bag. Penyakit Dalam
Fakultas Kedokteran Universitas Hasanuddin
Makassar, Sulawesi Selatan
Penyebab MALARIA pada manusia : 5 jenis plasmodium
• P. Vivax : Malaria vivax ( demam tiap 3 hari)• P. Falciparum : Malaria falsiparum ( demam tiap 24 - 48
jam )• P. Malariae : Malaria malariae/ quartana ( demam tiap 4
hari )• P. Ovale : Malaria ovale ( seperti vivax )• P. knowlesi ( dahulu menginfeksi binatang, demam tiap
hari) )
GEJALA - PRODROMAL
• Kelesuan ( malaise )• Sakit kepala• Sakit belakang• Nyeri tulang/ otot• Anorexsia• Perut tak enak• Diarea ringan• Merasa dingin di punggung
Gejala Malaria
• Karakteristik : Demam periodik, Anemia, Splenomegali
Demam periodik ( “ Trias Malaria “ ):– Dingin/ menggigil ( 15 - 60 menit )
– Panas ( 1 - 2 jam )
– Berkeringat
Periode bebas demam 12jam(P.F), 36(P.V), 72(P.M), 24(P.K)
• Sakit kepala• Gejala gastro-intestinal : mual & muntah, nyeri
epigastrium• Non-spesifik : diarea, batuk
P. Vivax P. Malariae
P. Falciparum
DISEASE COURSE OF MALARIA INFECTION :
PRIMARY ATTACK, LATEN PERIOD, RECRUDENSE RELAPS.
MALARIA VIVAX• M. TERTIANA, Benigna ?, inkubasi 12 - 20 hari• Serangan demam sore hari• Manifestasi klinis bisa ringan - berat• Splenomegali H 4 - 5• Mortalitas rendah-tinggi, morbiditas tinggi• Gejala prodromal ringan• Demam ireguler 2-4 hari, menjadi intermiten• Herpes pada bibir hilang setelah OAM• Anemia sering pada anak-anak• Penderita semi-imun gejala tidak spesifik32.0
MALARIA OVALE
• Bentuk paling ringan• Inkubasi 11 - 16 hari, periode laten 4 tahun• Terjadi infeksi ganda, P. ovale tak tampak• Gejala klinis seperti vivax, lebih ringan, puncak panas
lebih rendah dan lama demam lebih pendek• Dapat sembuh spontan tanpa obat• Menggigil jarang, splenomegali jarang
MALARIA MALARIAE
• Malaria Quartana• Banyak di Afrika & Amerika Latin• Inkubasi 18 - 40 hari• Gejala ringan, insidious, nausea, muntah, herpes
labialis, anemia jarang.• Parasitemia sebelum gejala demam• Splenomegali sering hanya ringan• Komplikasi jarang, dapat terjadi sindroma nefrotik
• Malaria Tropika, inkubasi 9 -14 hari• Bentuk paling berat: sering anemia, panas ireguler,
splenomegali dan parasitemia• Sering demam tinggi > 40 C• Gejala prodromal lebih sering• Sering menimbulkan komplikasi ( M. berat ): kejang,
serebral, ikterus, ggl ginjal.• Splenomegali lebih cepat, sering pada minggu I, nyeri
pada perabaan.• Parasitemia dapat tinggi
MALARIA FALSIPARUM
PLASMODIUM KNOWLESIThe “ Fifth “ Malaria
• Dulu hanya menginfeksi kera (Macaca Mullata)
• Sejak th 2004 dilaporkan retrospeksif di Serawak
• Vector Anopheles leucosphyrus group (An. Laten,
cracens)
• Misdiagnosis sebagai malaria malariae, mikroskopik
menyerupai P. malariae
PLASMODIUM KNOWLESIThe “ Fifth “ Malaria
• Klinis TIDAK seperti malariae, demam tiap 24 jam,
diarea, nyeri abdomen dan ditemukan
hiperparasitemia > 250.000/uL
• Dapat memberikan komplikasi ikterik, hipotensi, gagal
ginjal, serebral dan gagal pernafasan
• Diagnosa pasti identifikasi dengan PCR
Malaria Knowlesi
Pasien malaria.. Menggigil, berselimut lengkap
No. Gejala Klinik N % -ase
1. Splenomegali 203 24.2
2. Keluhan Abdominal 200 23.9
3. Hepatomegali 133 15.9
4. Ikterus 78 9.3
5. Hepatomegali + Ikterus 54 6.5
6. Kelainan serebral 32 3.8
7. Kelainan ginjal 23 2.7
8. Abortus 2 0.2
9. Edema paru 1 0.1
Gambaran klinik 836 kasus malaria di RSU Bethesda ‘83 -’85
MALARIA KEHAMILAN
• Sering dialami ibu daerah endemik• Sering dijumpai pada trimester I & II, pada malaria
berat trimester II & III• Penyebab: penurunan imunitas ( steroid/ gonadotropin
naik )• Akibat : abortus, penulit partus (anemia), BB bayi
rendah, IUFD, partus prematurus, • Malaria berat ( hipoglikemia, edema paru , ggl ginjal,
mal. kongenital
PLACENTAL MALARIA
• Parasite/ malaria pigment (haemozoin) in placental blood
• Maternal Anemia• Low Birth weight• Pre-term delivery• Increased Perinatal/ Infant mortality• Highly endemic area Asymptomatic
MALARIA POST TRANSFUSI DARAH• Akibat donor terinfeksi malaria• Screning donor daerah endemik sulit• Parasit masih hidup dalam donor 1 minggu• Komponen darah dalam cryopreserved dapat hidup 2
tahun.• Inkubasi bervariasi : tergantung derajat parasitemia dan
imunitas resipien.• Umumnya 16 - 23 hari. ( P. falciparum 8 -29 hari & P.
vivax : 8 30 hari )• Setelah 3 bulan post-transfusi, demam periksa untuk
malaria
MALARIA CAMPURAN
• Infeksi Plasmodium campuran
• Sering P. Falciparum & P. Vivax
• Infeksi 3 atau 4 Plasmodium jarang.
• Dalam pemeriksaan sering saling menutupi
• Bila malaria berat ditemukan P vivax, harus diperiksa
ulang karena sering terjadi infeksi campuran.
MALARIA KRONIK
• Sering terjadi di daerah endemik
• Transmisi yang berulang-ulang
• Splenomegali yang besar
• Anemia, BB turun, pucat, kurus, kulit kering, dehidrasi ( malaria cachexia )
• Anak sering gangguan pertumbuhan
• Ibu hamil sering abortus & gangguan sterilitas
400 GigitanNyamuk
200 Meng-infeksi
Manusia
100 MalariaKlinis
2 – 6 %Malaria Berat
MALARIA BERAT
• MALARIA SEREBRAL• ANEMIA BERAT HB < 5 gr% / Ht < 15% + parasit > 10000• GAGAL GINJAL AKUT < 400 ml/24 jam & Kreat > 3 mg% • EDEMA PARU / ARDS• HIPOGLIKEMI < 40 mg%• SYOK SISTOLIK < 70 mmHg / Anak < 50 mmHg• PERDARAHAN SPONTAN / DIC• KEJANG BERULANG > 2 x/ 24 jam• ASIDOSIS Ph <7.25 , Plasma Bicarb < 15 mmol/L• HAEMOGLOBINURIA• HIPERPARASITEMIA > 5 %• MALARIA DGN BILIRUBIN > 3 MG% + gagal Organ lain• HIPERTERMIA > 40 C (Oral)
Ditemukan Aseksual Plasmodium F/V/K, dengan salah satu :
SEVERE MALARIA
DEFINITION : Patient, Plasmosium Asexual parasitemia,with one or more CLINICAL or LABORATORY FEATURES :
PROSTRATION
IMPAIRED CONSCIOUSNESS
RESPIRATORY DISTRESS
MULTIPLE CONVULSIONS
CIRCULATORY COLLAPSE
PULMONARY EDEMA
ABNORMAL BLEEDING
JAUNDICE
HAEMOGLOBINURIA
SEVERE ANAEMIA
HYPOGLYCAEMIA
ACIDOSIS
RENAL IMPAIRMENT
HYPERLACTATAEMIA
HYPERPARASITEMIA
WHO: Guidelines for the Treatment of Malaria 2006
BEDA MALARIA BERAT PADA DEWASA & ANAK
A N A K DEWASA
Batuk Sering JarangKejang Sangat sering SeringIkterik Jarang SeringLama sakit Pendek (1-2 hr)Panjang (5-7 hr)Lama koma Pendek (1-2 hr)Panjang (2-4 hr)Hiperparasitemia Sering JarangHipoglikemia Sering sebelum Rx Sering sesudah Rx/HmlGagal ginjal Jarang SeringTek.I.K naik Sering/naik Jarang/ normalEdema paru Jarang SeringPerdarahan Jarang ---10 %Ggn brain stem Lebih sering JarangSequelae Neuro. > 10 % < 5 %
Plasmodium Falciparum, Vivax, Knowlesi dapat menyebabkan Malaria Berat
Kematian10 – 50 %
2-- 6%
Syndromes of severe malaria: 1. Children
1. Severe anemia2. Metabolic acidosis3. Cerebral malaria
Exacerbated by:• hypovolemia• hypoglycemia• salicylate toxicity
• Renal failure rare• Lung injury/ARDS rare
Syndromes of severe malaria: 2. non-immune adults
Multiorgan failure:– Hyperparasitemia – Acute renal failure– Jaundice– Metabolic acidosis– Hypoglycemia– Acute respiratory distress
syndrome– Anemia/thrombocytopenia– Cerebral malaria
Prognostic value & frequency of SM in adults / children
Children ChildrenAdults AdultsClinical manifestations or
Laboratory finding
Prostration
Impaired counciousness
Respiratory distress ( acidotic breathing )
Multiple convulsions
Circulatory collapse
Pulmonary Edema (radiological)
Abnormal bleeding
Jaundice
Haemoglobinuria
Severe Anemia
+
+
+++
+ +
++
+
+ ++
+
++
+
+
+
+ / -+ / -
+ / -
+++++++++
+++
++++++
+++
+++
+++++++++
+++
+++
+++
++++
++
++
++
?
Classifications SM in Children• Group 1: (require parenteral Rx & Support.Tx )Group 1: (require parenteral Rx & Support.Tx )
1. Prostration ( inability to sit upright), 3 subsgroup :• Prostrate but fully concious
• Prostrate with impaired conciousness not coma
• C o m a
2. Respiratory distress ( acidotic breathing• Mild – nasal flaring &/ or mild intercostal indrawing
• Severe – mark intercoctal indrawing or deep acidotic
• Group 2 (able to take oral Rx, require supervised) :Group 2 (able to take oral Rx, require supervised) :1. Haemoglobin < 5 gr% or haematocrit < 15%
2. > = 2 convulsions in 24 hours
• Group 3 : require parenteral Tx because of persistent vomiting, Group 3 : require parenteral Tx because of persistent vomiting, not in group 1 or 2.not in group 1 or 2.
DIAGNOSIS OF 114 CASES SEVERE MALARIA in Emergency Unit
Bethesda Hospital Tomohon
DIAGNOSIS OF 114 CASES SEVERE MALARIA in Emergency Unit
Bethesda Hospital Tomohon
• Sepsis 1 %Sepsis 1 %• Nephrolithiasis 1%Nephrolithiasis 1%• Syncope 1%Syncope 1%• Epilepsy 1%Epilepsy 1%
Severe Malaria 48 (42%)Severe Malaria 48 (42%) Clinical Malaria 35 (31%)Clinical Malaria 35 (31%) Stroke 7 (6%)Stroke 7 (6%) Hepatitis 5 (4%)Hepatitis 5 (4%) Typhoid fever 4 (3.5%)Typhoid fever 4 (3.5%) Gastritis 3 (2.6%)Gastritis 3 (2.6%) Liver absces 2 (2%)Liver absces 2 (2%) Pneumonia 2 (2%)Pneumonia 2 (2%) Dehydration 1%Dehydration 1% Pharyngitis 1%Pharyngitis 1% Chronic Renal Failure 1%Chronic Renal Failure 1% Urinary Tract Infection 1%Urinary Tract Infection 1%
Malaria cerebral 25 (52%)Malaria + jaundice 22 (46%)Malaria + ARF 1 (2%)
Malaria + jaundice 16 (46^)Malaria + ARF 9 (26%)Malaria cerebral 6 (17%)Hyperparasitemia 3 (11%)
RELATIONSHIP BETWEEN ORGAN RELATIONSHIP BETWEEN ORGAN INVOLVEMENT AND MORTALITY in Severe INVOLVEMENT AND MORTALITY in Severe
MalariaMalaria
RELATIONSHIP BETWEEN ORGAN RELATIONSHIP BETWEEN ORGAN INVOLVEMENT AND MORTALITY in Severe INVOLVEMENT AND MORTALITY in Severe
MalariaMalaria
010.5
47.6
88.9100
0
20
40
60
80
100
0 1 2 3 4
Mortality
DEFINITIONDEFINITIONDEFINITIONDEFINITION
PRACTICAL :PRACTICAL :
IMPAIRMENT OF CONSCIOUSNESS OR CONVULSION IN IMPAIRMENT OF CONSCIOUSNESS OR CONVULSION IN PATIENT EXPOSED TO MALARIAPATIENT EXPOSED TO MALARIA
RESEARCHRESEARCH
AN UNROUSABLE COMA MORE THAN 30 MINUTES, AN UNROUSABLE COMA MORE THAN 30 MINUTES, POSITIVE MALARIA SMEAR, WITHOUT OTHER POSITIVE MALARIA SMEAR, WITHOUT OTHER CAUSES ENCEPHALOPATHYCAUSES ENCEPHALOPATHY– GCS : < 11 /15 or 9 / 11GCS : < 11 /15 or 9 / 11
PRACTICAL :PRACTICAL :
IMPAIRMENT OF CONSCIOUSNESS OR CONVULSION IN IMPAIRMENT OF CONSCIOUSNESS OR CONVULSION IN PATIENT EXPOSED TO MALARIAPATIENT EXPOSED TO MALARIA
RESEARCHRESEARCH
AN UNROUSABLE COMA MORE THAN 30 MINUTES, AN UNROUSABLE COMA MORE THAN 30 MINUTES, POSITIVE MALARIA SMEAR, WITHOUT OTHER POSITIVE MALARIA SMEAR, WITHOUT OTHER CAUSES ENCEPHALOPATHYCAUSES ENCEPHALOPATHY– GCS : < 11 /15 or 9 / 11GCS : < 11 /15 or 9 / 11
Glasgow Coma ScaleGlasgow Coma Scale• Respon mata : spontan 4
dgn suara 3dgn nyeri 2tak ada reaksi 1
• Respon Bicara : normal respon 5bingung 4berkata kacau 3suara merintih 2tak ada suara 1
• Respon motorik : gerakan normal 6dapat melokalisir nyeri 5fleksi thdp nyeri 4extensi 3decerebrate rigidity 2tak ada reaksi 1
TOTAL 3 -- 15
Blantyre Coma Scale (modifikasi)Blantyre Coma Scale (modifikasi)
• Respon mata :
mengikuti wajah ibu 1tak ada reaksi 0
• Respon Bicara : menangis wajar 2
menangis merintih 1tak ada suara 0
• Respon motorik : melokalisir nyeri 2
menarik anggota o.k. nyeri 1
tak ada reaksi 0
TOTAL 0 --7
Extensi pada malaria cerebral
CLINICAL MANIFESTATION
NEUROLOGICAL SYNDROME : DIFFUSE, POTENTIALLY RAPIDLY REVERSIBLE ENCEPHALOPATHY ASSOCIATED WITH LOSS OF CONSCIOUSNESS AND FITTING– mild meningism, no neck rigidity– dysconjugate gaze– vertical nystagmus– N.VI palsy– doll’s eye, oculovestibular reflex normal response– symetri UMN, increased tone & jerk, clonus, extensor– plantar response + , brisk Jaw jerk– pout reflex + , abdominal reflex -, cremasteric reflex + .– cerebellar sign present
Malaria Retinopathy
Penelitian pada malaria berat orang dewasa di Bangladesh menunjukkan retinopati pada 63% sedangkan pada malaria serebral 70%. Retinopati derajat sedang sampai berat lebih banyak dijumpai pada malaria serebral. Beratnya pemutihan retina berkorelasi dengan kadar plasma laktat, hal ini diduga berhubungan dengan adanya iskemia pada retina karena obstruksi mikrovaskuler.
DIFFERENTIAL DIAGNOSIS CM
•INFECTION :• MENINGITIS, •ENCEPHALITIS, •TYPHOID FEVER, •SEPTIC SHOCK
•STROKE & HEAD INJURY•METABOLIC COMA•ECCLAMPSIA•ALCOHOLISM , INTOXICATION
Diagnosis & management important start from emergency unit
8 hours after admission
24 hoursafter admission
Ikterik & Cerebral
Malaria cerebral , jaundice, in Manado General Hospital
GANGGUAN FAAL HATI PADA MALARIA BERAT
• IKTERIK SERING DIJUMPAI ( RINGAN - BERAT )
• IKTERIK TERGANTUNG JUMLAH PARASIT• IKTERIK ( HEMOLISIS / DISFUNGSI HATI )• “ BILIOUS REMITENT FEVER “
( IKTERIK, HIPERPARASITEMIA, SEREBRAL & GAGAL GINJAL “ Algid Malaria” )
• AKIBAT: - Hipoalbuminemia
- Gangguan koagulasi
- Penurunan klirens
HIPOGLIKEMIA
• Bila gula darah < 40 mg%• Sering dijumpai pada ibu hamil ( primi-
gravida)• Pada anak-anak sering sebelum pengobatan• Pada orang dewasa sering terjadi sesudah
pengobatan kina ( 3 jam post terapi kina )
Patogenesa Hipoglikemia• Parasit memerlukan karbo-hidrat untuk
metabolismenya• Pada malaria dengan hiperbilirubin aemia, terjadi
kegagalan glukoneogenesis• Kina menstimuli produksi insulin ( hiperinsulinemia )• Peningkatan Tumor Necrosis factor ( TNF-alfa )
ACUTE KIDNEY INJURY (AKI)
• Malaria related Acute Kidney Injury (MAKI)
• Penurunan fungsi ginjal dalam 48 jam :– Peningkatan serum kreatinin 0.3 mg/dL, atau– Peningkatan serum kreatinn 50% dan nilai dasar, atau– Penurunan urin output 0.5 ml/kg/jam untuk 6 jam
• WHO : serum kreatinin > 3 mg/dL
• Sering pada malaria dewasa dan jarang pada anak
ACUTE RENAL FAILURE IN SEVERE MALARIA
PRE-RENAL RENAL
Urine S.G >1.020 <1.010Urine Osm. >500 <350(mOsm/kg H2O)Urine Na (meq/L) <10 >20Plasma BUN/Creatinine >15:1 <10-15:1U/P Urea >20:1 <10:1U/P Creatinine >40:1 <10:1U/P Osmolarity >2:1 <1:1Renal failure Index <1 >1Fractional excretion of filtered Na <1 >1
• Faktor untuk mempermudah MAKI :– Kehamilan– Parasitemia tinggi– Ikterik yang tinggi– Dehydrasi– NSAID
• Faktor yang penting prognosa MAKI– Hipovolemia/ hipervolemia– Hiperparasitemia– Hemoconcentrasi– Hiperbilirubinemia– Hiperpireksia
• 2 Types of Pulm.Oedema :2 Types of Pulm.Oedema :
* Overload pulm.oedema* Overload pulm.oedema
* ARDS* ARDS
Pulmonary Oedema in sev.malaria
PULMONARY MANIFESTATION IN MALARIA
• Historically :– Bronchitic– Pneumonic– Bronchopneumonic
• Acute Lung Injury (ALI)
• Acute Respiratory Distress Syndrome (ARDS)
Pulmonary Oedema in sev.malaria
Dehydration Overhydration
Low jugular venous pressureSkin tentingPostural dizzinessPostural blood pressure drop
of 15 mmHgTachycardiaMuscle cramps
Jugular venous distentionPitting oedemaHypertensionRalesCardiomegalyThird heart soundProgressive dyspneaOrthopneaNocturnal cough
A.R.D.S
• Occurs in P. Falciparum, P. Vivax, P. Ovale & ? P. Knowlesi
• Common in adult than children, pregnancy and non-immune
• Mechanism : Increased alveolar cappilary permeability intravascular fluid loss into the lungs
• Presentation : initial presentation or after initiation treatment
• Clinical : acute onset dyspnea respiratory failure
CLINICAL FINDING• Manifest abrupt onset dyspnoea, cough, tightness in the chest that
progresses rapidly over a few hours
• Disorientation and agitation is frequently present.
• Physical examination : signs of respiratory distress ( air hunger, use of accessory muscles of respiration, suprasternal and intercostal indrawing ), central and peripheral cyanosis (arterial hypoxaemia), basal crepitations and expiratory wheezing.
• In these patients, high parasitaemia,acute renal failure, hypoglycemia, metabolic acidosis, disseminated intravascular coagulation (DIC), and bacterial sepsis usually co-exist.
Chest radiography :• Bilateral frontal opacities (alveolar pattern),
increased interstitial markings
• The cardiac size is usually normal
• Rarely, thickening of lung fissures, interlobular septal lines
• Pleural effusion
• In assisted ventilator :– complications pneumothorax, pneumomediastinum ,
pneumonia may occur
Definisi ARDS :Gagal respirasi berat
Pa O2↓(<70torr) IPPB F1O2 50%
Faktor Predisposisi :
Hiperparasitisme
Gagal ginjal
Kehamilan / post partum
Hipoglikemi
Asidosis metabolik
Malaria serebral
Kelebihan cairan
ANEMIA BERAT• Hb. < 5 gr% atau Ht < 15 %
• Parasit > 10.000 par/ uL
• Bukan thallasemia, iron deffeciency atau keadaan lain yang dapat menyebabkan anemia.
Malaria dengan perdarahan:• Gejala: perdaraha gusi,petikie, hematom,
epiktaksi, perdarahan sub conjungtiva.
• Tanda: anemia, trombositosis, koagulopati, KID >10%.
Berhubungan dengan : edema paru, ikterik, hiperparasitemia
A child, 5 months, malaria falciparum ++++, Hb. 1.6 gr%
In RSMM-Timika Hospital, Papua
MM4-1
Perdarahan pada malaria berat : Hematom di pipi
Purpura ( perdarahan dibawah kulit, pada malaria dengan trombosit 2000/ mm3
Asidosis metabolik:
• Nafas kusmoul, auskultasi paru N
• Kadar asam laktet
• pH serum < 7,2
• Bikarbonat rendah (<15 ml/l)
• Berkaitan dengan : edema paru, hiperparasitemia, syok, gagal ginjal, hipoglikemia.
.. Silahkan bertanya, malu bertanya sesat dijalan …….