Diagnosis Dini dan Penatalaksanaan Malaria

MALARIAMALARIA ESSENTIALS OF DIAGNOSISESSENTIALS OF DIAGNOSIS HISTORY OF EXPOSURE IN A MALARIA-ENDEMIC HISTORY OF EXPOSURE IN A MALARIA-ENDEMIC

AREAAREA PERIODIC ATTACTS OF SEQUENTIAL CHILLS, FEVER PERIODIC ATTACTS OF SEQUENTIAL CHILLS, FEVER

& SWEATING, APYREXIA& SWEATING, APYREXIA HEADACHE, MYALGIA, SPLENOMEGALI, ANEMIA, HEADACHE, MYALGIA, SPLENOMEGALI, ANEMIA,

LEUKOPENIALEUKOPENIA PARASITES IN RBC, IDENTIFIED IN THICK OR THIN PARASITES IN RBC, IDENTIFIED IN THICK OR THIN

BLOOD FILMSBLOOD FILMS

ETIOLOGY : ETIOLOGY : SPOROZOA GENUS SPOROZOA GENUS

PLASMODIUMPLASMODIUMPlasmodia malaria :Plasmodia malaria : Pl. vivax Pl. vivax Mal. tertiana benigna Mal. tertiana benigna Pl. ovale Pl. ovale Mal. ovale / T. benigna Mal. ovale / T. benigna Pl. falsiparum Pl. falsiparum Mal. tropika / T. maligna Mal. tropika / T. maligna Pl. malariae Pl. malariae Mal. Kuartana Mal. Kuartana P. knowlesi ( dahulu menginfeksi binatang, P. knowlesi ( dahulu menginfeksi binatang,

demam tiap hari) demam tiap hari) perbatasan dgn perbatasan dgn MalaysiaMalaysia

Life cycle of malaria Life cycle of malaria parasitesparasites

P falciparum life cycleP falciparum life cycle

LIFE CYCLE OF MALARIA PARASITESLIFE CYCLE OF MALARIA PARASITESEE I

EE II

Exoerytrocyter & RBC phase Exoerytrocyter & RBC phase of Pl. malariaof Pl. malaria

Pl. vivaxPl. vivaxEE II (+)EE II (+)

Pl. ovalePl. ovale EE I (+) EE I (+)

Pl. falcifarumPl. falcifarum EE II (-) EE II (-)

Pl. malariaePl. malariae

EE II: HeparEE II: Hepar EE I : Dlm darah menuju ke hati EE I : Dlm darah menuju ke hati

PATHOGENESIS (1) XXX THE ASEXUAL ERYTHROCYTIC IS RESPONSIBLE FOR THE

SYMPTOMS:

- FEVER, HEADACHE, NAUSEA & MUSCULAR PAIN

AT THE TIME SCHIZONTINFECTED RBC RUPTURE

- ENDOGENEOUS PYROGEN (INTERLEUKIN-1) AND

MEDIATORS (KININS & CATHECTIN (TNF) RELATED

TO PATHOGENESIS?

PATHOGENESIS (2) XXX * ENCEPHALOPATHY:

~ RBC CONTAINING SCHIZONTS & MALARIAL

PIGMENT OBSTRUCT CEREBRAL CAPILLARIES &

VENULES

~ CEREBRAL EDEMA MAY DEVELOP AS A RESULT

OF AGONAL HYPOXIA

~ SEQUESTRATION OF PARASITIZED RBC IN BRAIN

& OTHER TISSUE RESULT FROM CYTOADHERENCE

OF KNOBLIKE PROTUBERANCE ON THE RBC TO

ENDOTHELIUM

PATHOGENESI (3) XXX

~ DECREASED DEFORMITY OF INFECTED RBC

SLUGGISH MICROVASCULAR FLOW

~ CEREBRAL ANAEROBIC GLYCOLYSIS & REDUCED

CEREBRAL OXYGEN TRANSPORT CEREBRAL

MALARIA

PATHOGENESIS (4) XXX

- ANEMIA:~ HEMOLYSIS OF INFECTED RBC~ RAPID SPLENIC REMOVAL ON NONPARASITIZED

ERYTHROCYTES~ DYSERYTHROPOISIS

- THROMBOCYTOPENIA SEQUESTRATION IN THE SPLEEN

PATHOGENESIS (5) XXX

- ACUTE RENAL FAILURE

ACUTE TUBULAR NECROSIS

ISCHEMIA RESULTING FROM:

~ HYPOVOLEMIA

~ RENAL VASOCONTRICTION

~ MICROVASCULAR OBSTRUCTION:

* PARASITIZED RBC

* PIGMENT NEPHROPATHY SECONDARY

TO HEMOLYSIS

ACUTE RENAL FAILURE

Diagnosis malariaDiagnosis malaria• Ada riwayat demam sebelumnya 3 Ada riwayat demam sebelumnya 3

harihari• Tidak ada penyebab yang lainTidak ada penyebab yang lain• Ada gambaran klinis: Ada gambaran klinis: Dingin Dingin Demam Demam

Keringat -- Apireksia Keringat -- Apireksia • Ditemukan adanya anemiaDitemukan adanya anemia• Diagnosis parasitologis semestinya sdh ada Diagnosis parasitologis semestinya sdh ada

dalam wkt < 2 jamdalam wkt < 2 jam– Light microscopicLight microscopic– RDT (Rapid Diagnostic Test )RDT (Rapid Diagnostic Test )

PATHOGENESIS (6) XXX•THE SPLEEN IS LARGE:

~ ENGORGE & HEAVILY PIGMENTED

~ CONTAINING MANY PHAGOCYTIC CELLS

INGESTED RBC & MALARIAL PIGMENT

* EDEMATOUS LUNGS:

~ PULMONARY CAPILLARIES & VENULE ARE

PACKED WITH INFLAMMATORY CELLS

~ ENDOTHELIAL & INTESTINAL EDEMA

Pembesaran Lien menurut Pembesaran Lien menurut HackettHackett

Pembesaran Lien menurut Pembesaran Lien menurut SchuffnerSchuffner

CLINICAL FINDINGS (1)A. SYMPTOMS (1)

- SHAKING CHILLS (THE COLD STAGE)

- FEVER (THE HOT STAGE) ≥41ºC

- DIAPHORESIS (THE SWEATING STAGE)

- FATIGUE

- HEADACHE

- DIZZINESS

- MYALGIA

- ARTHRALGIA

- BACKACHE

- DRY COUGH

DINGIN DEMAM

APIREKSI KERINGAT

DI-DE-RI-TA

KASUS MALARIAKASUS MALARIA Kasus tanpa komplikasiKasus tanpa komplikasi Malaria berat atau malaria dengan Malaria berat atau malaria dengan

komplikasikomplikasi Kasus Rujukan ke rumah sakitKasus Rujukan ke rumah sakit

Kasus tanpa komplikasiKasus tanpa komplikasi Mesti dibedakan dengan:Mesti dibedakan dengan:

– Demam tifoidDemam tifoid– Demam dengueDemam dengue– Infeksi saluran napas akutInfeksi saluran napas akut– Leptospirosis ringanLeptospirosis ringan– Infeksi virus yang lain Infeksi virus yang lain

Demam tifoidDemam tifoid1.1. Demam sore/malam hari (naik Demam sore/malam hari (naik

perlahan-lahan)perlahan-lahan)2.2. Lidah tifoidLidah tifoid

- Kering di lidahaKering di lidaha- TremorTremor- Pinggir hiperemisPinggir hiperemis- Di tengah kotor ke abu-anuanDi tengah kotor ke abu-anuan

3.3. Nyeri tekan kanan bawah > kiri bawahNyeri tekan kanan bawah > kiri bawah

Demam berdarah dengueDemam berdarah dengue1.1. Gangguan gastrointestinalGangguan gastrointestinal2.2. Mata: - hiperemis, rasa nyeri Mata: - hiperemis, rasa nyeri

retroorbitalretroorbital3.3. Demam datang tiba-tiba langsung Demam datang tiba-tiba langsung

tinggitinggi4.4. --------------5.5. Demam Demam baru rasa dingin baru rasa dingin

Malaria berat atau malaria Malaria berat atau malaria dengan komplikasidengan komplikasi

Perlu dibedakan dengan infeksi lainPerlu dibedakan dengan infeksi lain Radang otak (meningitis, ensefalitis)Radang otak (meningitis, ensefalitis) Stroke (gangguan serebrovaskuler)Stroke (gangguan serebrovaskuler) Tifoid ensefalopatiTifoid ensefalopati HepatitisHepatitis Leptospirosis beratLeptospirosis berat Glomerulonefritis akut atau kronisGlomerulonefritis akut atau kronis SepsisSepsis DBD atau dengue shock syndrome/DSSDBD atau dengue shock syndrome/DSS

Kasus Rujukan ke rumah Kasus Rujukan ke rumah sakitsakit

– Semua kasus berat atau berkomplikasi Semua kasus berat atau berkomplikasi segera dirujuk ke rumah sakitsegera dirujuk ke rumah sakit

– Semua kasus ringan yang sulit diatasiSemua kasus ringan yang sulit diatasi

Gejala klinis pokok Gejala klinis pokok malaria adalahmalaria adalah

– A. Menggigil/rasa dingin menyusul (1)A. Menggigil/rasa dingin menyusul (1)– B. Demam, menyusul (2)B. Demam, menyusul (2)– C. Kerkeringat banyak, menyusul (3)C. Kerkeringat banyak, menyusul (3)– ApireksiaApireksia

A-C disebutA-C disebut trias malaritrias malari

Klinis Malaria Klinis Malaria TRIAS MALARIA TRIAS MALARIA KOPAPDIKOPAPDI

DIDINGIN DNGIN DEEMAMMAM

((TATA)APIREKSI KE)APIREKSI KERIRINGATNGAT

DI-DE-RI-TADI-DE-RI-TA

Tanda klinis/ Trias Tanda klinis/ Trias Malaria/WHOMalaria/WHO

1. Anemis1. Anemis

2. Splenomegali2. Splenomegali

3. DIDERITA/ Trias KOPAPDI3. DIDERITA/ Trias KOPAPDI

Anemia• Pengrusakan eritrosit o/ parasit baik eritrosit yang terinfeksi parasit maupun tidak • Terjadi hambatan eritropoesis sementara • Hemolisis karena proses complement mediated immune system• Eritrofagositosis• Penghambatan pengeluaran retikulosit

Anemia pd P. falcifarum : suatu mekanisme multifaktorial dengan elemen destruksi meningkat & delektif produksi eritrosit

Pd pasien ini anemia jg diperberat: kehamilan & partus

Prosedur pasca perawatan Prosedur pasca perawatan kasuskasus

– Pada malaria Pada malaria tertianatertiana di luar rumah sakit di luar rumah sakit

masih harus minum masih harus minum primakuinprimakuin selama selama 1515 hari hari

– Pada malaria Pada malaria tropikatropika umumya sembuh umumya sembuh

sempurna, kecuali ada sekuelae dari sempurna, kecuali ada sekuelae dari

komplikasikomplikasi

Malaria berat (salah Malaria berat (salah satunya)satunya)

Tanda-tanda Laboratorium1. Gangguan kesadaran ringan (GCS <15) malaria serebral

7. Anemia berat (Hb < 5 gr% atau hematokrit <15%

2. Kelemahan otak (tidak bisa duduk/berjalan) tanpa kelainan neurologik

8. Pada hitung parasit 10.000/µL

3. Kejang-kejang 9. Asidemia asidosis?4. Perdarahan spontan 10. Makroskopik

hemoglobinuri5. Gagal ginjal akut: urine <400ml / 24 jam

11. Hiperparasitemia >5%

6. Hiperpireksia (suhu rektal >400C)

12. Ikterus (kadar bilirubin darah > 3 mg%)

BEDA MALARIA BERAT PADA DEWASA & ANAKBEDA 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 %

BEDA MALARIA BERAT PADA ANAK DAN BEDA MALARIA BERAT PADA ANAK DAN DEWASADEWASA

Items Anak DewasaBatuk 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 Jarang

Hipoglikemia Sering sebelum Rx Sering sesudah Rx/hml

Gagal ginjal Jarang SeringTek.I.K naik Sering naik Jarang/normalEdema paru Jarang SeringPerdarahan Jarang 10%Ggn brain stem Lebih sering JarangSequelae Neuro. > 10% < 5%

SEVERE MALARIASEVERE MALARIA

DEFINITION : Patient, Plasmosium Asexual parasitemia,with one or more CLINICAL or LABORATORY FEATURES :

PROSTRATIONIMPAIRED CONSCIOUSNESSRESPIRATORY DISTRESSMULTIPLE CONVULSIONSCIRCULATORY COLLAPSEPULMONARY EDEMAABNORMAL BLEEDINGJAUNDICEHAEMOGLOBINURIA

SEVERE ANAEMIAHYPOGLYCAEMIAACIDOSISRENAL IMPAIRMENTHYPERLACTATAEMIAHYPERPARASITEMIA

WHO: Guidelines for the Treatment of Malaria 2006

CLINICAL FINDNGS (2)

SYMPTOMS (2)

- GASTROINTESTINAL SYMPTOMS:

~ ANOREXIA

~ NAUSEA

~ VOMITING

~ DIARRHEA

~ ABDOMINAL CRAMPS

CLINICAL FINDINGS (3)

SYMPTOMS (3)

-THE ATTACKS PERIODICITY:

~ EVERY-DAY FALCIPARUM

~ EVERY-OTHER-DAY TERTIAN PL. VIVAX & OVALE

~ EVERY-THIRD-DAY QUARTIAN PL. MALARIAE

~ TIRED BETWEEN ATTACKS, BUT FEELS WELL

~ AFTER THIS PRIMARY EPISODE, RECURRENCE ARE

COMMON, EACH SEPERATED BY A LATENT PERIOD

CLINICAL FINDINGS (4)

SIGNS

- SPLENOMEGALY:

APPEAR ACUTE SYMPTOMS

CONTINUED ≥4 DAYS

- MILDY HEPATOMEGALY

- ANEMIA

COMPLICATIONS (1):1. CEREBRAL MALARIA:

- HEADACHE

- MENTAL DISTURBANCES

- NEUROLOGIC SIGNS

- RETINAL HEMORRHAGES

- CONVULSIONS

- DELIRIUM

- COMA

COMLICATIONS (2):

2. HYPERPYREXIA

3. HEMOLYTIC ANEMIA

4. NONCARDIOGENIC PULMONARY EDEMA

5. ACUTE TUBULAR NECROSIS & RENAL

FAILURE BLACKWATER FEVER DUE TO

>QUININE TREATMENT

COMPLICATIONS (3)6. ACUTE HEPATOPATHY MARKED

JAUNDICE, BUT NO LIVER FAILURE

7. HYPOGLYCEMIA

8. ADRENAL INSUFFICIENCY-LIKE SYNDROME

9. CARDIAC DYSRHYTHMIAS

10, GASTROINTESTINAL SYNDROMES

11. LACTIC ACIDOSIS & HYPOGLYCEMIA

12. PNEUMONIA

13. WATER & ELECTROLYTE IMBALANCE

Plasmodium Falciparum>>, Vivax, Knowlesi dapat menyebabkan Malaria Berat

Kematian10 – 50 %

2-- 6%

Malaria cerebral salah satu komplikasi malaria terberat,

berlangsung progresif

Plasmodium falciparum

25-50%

Kematian

P. Vivax P. Malariae

P. Falciparum

Pasien malaria.. Menggigil, berselimut lengkap

400 GigitanNyamuk

200 Meng-infeksi

Manusia

100 MalariaKlinis

2 – 6 %Malaria Berat

Syndromes of severe malaria: Syndromes of severe malaria: XXXXXX

2. non-immune adults2. non-immune adultsMultiorgan failure:Multiorgan failure:

– Hyperparasitemia Hyperparasitemia – Acute renal failureAcute renal failure– JaundiceJaundice– Metabolic acidosisMetabolic acidosis– HypoglycemiaHypoglycemia– Acute respiratory Acute respiratory

distress syndromedistress syndrome– Anemia/Anemia/

thrombocytopeniathrombocytopenia– Cerebral malariaCerebral malaria

Extensi pada malaria cerebral

8 hours after admission

24 hoursafter admission

Ikterik & Cerebral

Malaria cerebral , jaundice, in Manado General Hospital

Purpura ( perdarahan dibawah kulit, pada malaria dengan trombosit 2000/ mm3

Ny. S 36 tahunSuku Makassar

Alamat :Limbung, Sungguminasa GowaPekerjaan:ibu rumah tangga

masuk rumah sakit:Labuang Baji 03 September 2007 (reg. No.122153)

Apusan darah Tepi : Gambaran anemia hemolitik ec. Plasmodium falsiparum

EKG: dalam batas normal

Jawaban konsul subdivisi infeksi tropis Kesan: malaria cerebral Usul: Pemberian Kina intravena

Hasil Konsul Sub Divisi Hematologi-Onkologi Medik

Kesan : Anemia hemolitik belum dapat disingkirkanUsul : pemeriksaan bilirubin indirek, Coomb test, LDH, Retikulosit

Parameter Laboratorium

HARI 1 HARI 3 HARI 4

HARI 5

HARI 6

HARI 10

LeukositHbEritrositHematokritTrombositGDSUreum KreatininSGOTSGPTWidal DDR

3.9003.0-

10.267.00

0124

51005,7

2.14518,1

61.000

176231.92.0710447(-)(-)

-----------

(-)

1.500

7.0--

400085------

------

19.261.1----

5.7007.5

2.490-

179.000-

37.50.41

----

Parameter Laboratorium

HARI 1 HARI 3 HARI 4

HARI 5

HARI 10

LeukositHbEritrositHematokritTrombositGDSUreum KreatininSGOTSGPTWidal DDR

3.9003.0-

10.267.00

0124

51005,7

2.14518,1

61.000

176231.92.0710447(-)(-)

-----------

(-)

1.500

7.0--

400085------

5.7007.5

2.490-

179.000-------

MANAGEMENT: XXXA. TREATMENT OF ACUTE ATTACKS:

UNCOMPLICATED : SYMPTOMATIC WITHOUT SIGNS OF SEVERITY OR UNCOMPLICATED : SYMPTOMATIC WITHOUT SIGNS OF SEVERITY OR EVIDENCE OF VITAL ORGAN DYSFUNCTIONEVIDENCE OF VITAL ORGAN DYSFUNCTION (1)

1. ELIMINATION OF ASEXUAL ERYTHROCYTIC PARASITES

- CHLOROQUINE PHOSPHATE (SALT) 1G AT

0, 24, AND THEN 0.5 G AT 48 HOURS

HOURS 0 24 48

CHLOROQ/ GR 1 1 0.5 - MEFLOQUINE,

~ 1 x 250 MG FOR 3 DAYS, OR 750-1250 MG,

THEN 500 MG AFTER 6-8 HOURS

TREATMENT OF ACUTE ATTACKS (2) XXX

- QUININE SULFATE (PLUS DOXYCYCLINE, CLINDAMYCIN,

OR FANSIDAR

- ATOVAQUONE 250 MG (PLUS DOXYCYCLINE 100 MG OR

PROGUANIL 100 MG)

- HALOFANTRINE,

- ARTEMISININ (QINGHAOSU), FISRT DAY 2X2 TABS,

THEN 2X1 TABLET FOR 5 DAYS

TREATMENT OF ACUTE ATTACKS (3) XXX

IN SEVERE PATIENTS

- START ORAL THERAPY WITH CHLOROQUINE

AS SOON AS POSSIBLE

- IV QUININE DIHYDROCHLORIDE

- QUINIDINE GLUCONATE

- PARENTERAL CHLOROQUINE

TREATMENT OF ACUTE ATTACKS (4) XXX

2. ERADICATION OF P. VIVAX OR P. OVALE

CHLOROQUINE AS ABOVE FOLLOWED BY 0.5 G ON DAYS 10

AND 17 PLUS PRIMAQUINE PHOSPHATE, 25,3 MG (SALT)

DAILY FOR 14 DAYS STARTING ABOUT DAY 4

DAYS 1 2 3 4 10 17

CHLOROQ/G 1.0 1.0 0.5 ↓ 0.5 0.5

PRIMAQUINE 26.3 FOR 14 DAYS

TREATMENT OF ACUTE ATTACKS (5) XXX

3. ELIMINATION OF PERSISTENT GAMETOCYTEMIA

- CHLOROQUINE FOR P.VIVAX, P. OVALE,

P. MALARIAE

- PRIMAQUINE SALT, SINGLE DOSE, 26.3 MG

FOR P. FALCIPARUM

TREATMENT OF ACUTE ATTACKS (6) XXX

* TREATMENT OF FALCIPARUM MALARIA ACQUIRED

IN AREAS WHERE P. FALCIPARUM IS RESISTANT TO

CHLOROQUINE (1)

- START WITH ORAL QUININE SULFATE, 10 MG/KG 3X

DAILY FOR 3-7 DAYS, PLUS :

~ DOXYCYCLINE, 2X100 MG FOR 7 DAYS

~ CLINDAMYCIN. 3X900 MG DAILY FOR 5 DAYS

~ PYRIMETHAMINE, 2X25 MG DAILY FOR 3 DAYS

~ SULFADIAZINE, 4X500 MG DAILY FOR 7 DAYS

~ 3 TABLETS OF FANSIDAR (PYRIMETHAMIN+

SULFADOXINE)

TREATMENT OF ACUTE ATTACKS (7) P. FALCIPARUM IS RESISTANT TO CHLOROQUINE (2).

- ALTERNATIVE DRUGS ARE:

~ MEFLOQUINE

~ HALOPHANTRINE

~ ARTESUNATE

~ ATOVAQUONE

- SEVERELY ILL:

~ IV QUININE OR QUINIDINE

~ DOCYCYCLINE OR CLINDAMYCIN PARENTRALLY - ORAL TREATMENT WITH QUININE PLUS THE ANTIBIOTIC SHOULD BE AS SOON AS POSSIBLE - ARTESUNATEARTESUNATE++CLINDAMYCINECLINDAMYCINE //AZYTHROMICINEAZYTHROMICINE PREGNANT PREGNANT WOMAN & WOMAN & CHILDRENCHILDREN

TREATMENT OF ACUTE ATTACKS (8) * SPECIAL TREATMENT FOR TREATMENT OF SEVERE P. FALCIPARUM MALARIA (1) - MEDICAL EMERGENCY THAT REQUIRES:

~ HOSPITALIZATION~ INTENSIVE CARE~ IV CHEMOTHERAPY AS RAPID AS POSSIBLE~ REQUIRING >48 HOUR OF PARENTRAL THERAPY~ DEHYDRATION SHOULD BE DONE WITH CAUTION~ FLUID, ELECTROLYTE & ACID- BASE BALANCE

MUST BE MONITORED~ ArtesunateArtesunate + + Clindamycine Clindamycine / /AzytromicineAzytromicine

pregnant womanpregnant woman & & childrenchildren..

Di hidro artemicinine (DHA) plus Pipeaquine: Di hidro artemicinine (DHA) plus Pipeaquine: Artekin or Duo-cotexin (nearly recommended by Artekin or Duo-cotexin (nearly recommended by WHO.WHO.

TREATMENT OF ACUTE ATTACKS (9)* SPECIAL TREATMENT FOR TREATMENT OF

SEVERE P. FALCIPARUM MALARIA (2): ~ EARLY DIALYSIS MAY BE NECESSARY FOR RENAL

FAILURE

~ BLOOD GLUCOSE LEVELS SHOULD BE MONITORED

EVERY 6 HOURS IF HYPOGLYCEMIA +,

- 50% DEXTROSE, 1-2 ML/KG

- MAINTENANCE 5-10% DEXTROSE

TREATMENT OF ACUTE ATTACKS (10)* SPECIAL TREATMENT FOR TREATMENT OF SEVERE

P. FALCIPARUM MALARIA (3)

- DIC FRESH WHOLE BLOOD

- HCT < 20% TRANSFUSION

- EXCHANGE TRANSFUSION WHEN >15% RBC

ARE PARASITIZED

- SEIZURES ANTICONVULSANTS

- TEMPERATURE IS MAINTAINED <38.5 ºC

- BLOOD FILM SHOULD BE CHECKED DAILY UNTIL

PARASITEMIA CLEARS; WEEKLY THEREAFTER

FOR 4 WEEKS RECRUDESCENCE?

B. CHEMOPROPHYLAXIS (1)

a. IN REGIONS WHERE P. FALCIPARUM AND P. VIVAX

ARE SENSITIVE TO CHLOROQUINE

~ DRUG OF CHOICE

1. CHLOROQUINE PHOSPHATE, 500 MG WEEKLY, ONE

WEEK BEFORE ENTERING THE ENDEMIC AREA,

WHILE THERE, AND FOR 4-6 WEEK AFTER LEAVING

CHEMOPROPHYLAXIX (2) ~ ALTERNATIVE DRUGS

1. HALOFANTRINE.

2. FANSIDAR

3. AMODIAQUINE.

4. PYRIMETHAMINE

5. ARTEMISININ

6. PROGUANIL

7. QUININE

CHEMOPROPHYLAXIX (3)b. IN REGIONS WHERE P. FALCIPARUM IS RESISTANT

TO CHLOROQUININE

~ DRUGS OF CHOICE

1. MEFLOQUINE SALT, 250 MG (228 MG BASE) WEEKLY,

2 WEEKS BEFORE ENTERING THE ENDEMIC AREA,

WHILE THERE, AND FOR 4 WEEKS AFTER LEAVING.

CHEMOPROPHYLAXIX (4) ~ ALTERNATIVE:

- 1. DOXYCYCLINE, 100 MG DAILY, 2 DAYS BEFORE

ENTERING THE ENDEMIC AREA, WHILE THERE, AND FOR 4

WEEKS AFTER LEAVING (THIS DRUG AVAILABLE IN INDONESIA).(THIS DRUG AVAILABLE IN INDONESIA). - 2. MALARONE (ATOVAQUONE 250 MG + PROGUANIL 100

MG), ONE TABLET DAILY, ONE TABLET THE DAY BEFORE

ENTERING THE ENDEMIC AREA, WHILE THERE, AND FOR 1

WEEK AFTER LEAVING

CHEMOPROPHYLAXIX (5)- OTHER ALTERNATIVES:

DAILY PROGUANIL 200 MG + WEEKLY CHLOROQUINE

0.5 G, MORE PROTECTION THAN CHLOROQUINE

ALONE

CHEMOPROPHYLAXIX (6)c. PROPHYLAXIS FOR PREGNANT WOMEN

- THE BEST COURSE IS WEEKLY CHLOROQUINE +/– PROGUANIL - IN AREAS OF CHLOROQUINE-RESISTANT MALARIA

MEFLOQUININE, EXCEPT IN THE FIRST TRIMESTER

- DRUGS CONTRAINDICATED ARE DOXYCYCLINE &

PRIMAQUINE

PENGOBATAN MALARIAPENGOBATAN MALARIA

Golongan Jenis obatCinchona alkaloids Quinine4-aminoquinolines Chloroquine, amodiaquine

8-aminoquinolines Primaquine, tafenoquine, Pamaquine

4-quinoline methanols Mefloquine

9-phenanthrene methanols Halofantrine

Antifolic drugs Pyrimethamine, proguanil

Sulfa drugs a) sulphones; dapsone b) sulphonamides; sulphadoxine

Sesquiterpene lactones (Artemisinin derivatives)

a) artemisinin, dihydroartemisinin b) artesunate, artemether, arteether

Antibiotics Tetracycline, doksisiklin, chloramphenicol, Fluoroquinolon, azithromycin, clindamycin, rifampicin,

Combination 1. Artemether-lumefantrine (Coartem) ***2. Artesunate + amodiaquine3. Artesunate + mefloquine4. Artesunate + sulfadoxine-pyrimethamine ('Fansidar')

Riwayat resistensi obat Riwayat resistensi obat antimalariaantimalaria

ObatDiperkenalkan

Laporan pertama

resistensi

Beda waktu(tahun)

Quinine 1632 1910 278

Chloroquine 1945 1957 12

Mefloquine 1977 1982 5

Proguanil 1948 1949 1

Artemisinin 2000 2001 <1<1

Sulphadoxi-pyrimethamine (Fansidar)

1967 1967 0

Atovaquone 1996 1996 0

ACT ( Artemisinin Combination ACT ( Artemisinin Combination Treatment ) Treatment )

Artesunate + mefloquineArtesunate + mefloquine Artesunate + Sulphadoxine-PirimethamineArtesunate + Sulphadoxine-Pirimethamine Artesunate + PyronaridineArtesunate + Pyronaridine Artesunate-NaphthoquineArtesunate-Naphthoquine Artesunate + amodiaquine: Arsuamoon, ArtesdiaquineArtesunate + amodiaquine: Arsuamoon, Artesdiaquine Artemeter + lumefantrine ( COARTEM )Artemeter + lumefantrine ( COARTEM ) Dihydroartemisinin-Piperaquine(DHP), Arterekin, ArtepDihydroartemisinin-Piperaquine(DHP), Arterekin, Artep Dihydroartemisinin-Piperaquine-Trimetoprim (DPT)Dihydroartemisinin-Piperaquine-Trimetoprim (DPT) Dihydroartemisinin-Piperaquine-Trimetoprim, primaquine Dihydroartemisinin-Piperaquine-Trimetoprim, primaquine

(CV8)(CV8)

Kina HCl

•Obat anti malaria yang sangat efektif untuk semua jenis plasmodium •Efektif sebagai skizontosida maupun gametosida •Masih berefek kuat terhadap P. falcifarum yang resisten terhadap klorokuin.•Dapat diberikan dengan cepat dengan intra vena & cukup aman

Pemberian Pemberian Kina HCl Kina HCl Cara pemberian & dosis: Cara pemberian & dosis: Dosis loading 20 mg /kgBB Kina HCl dalam 100-200 Dosis loading 20 mg /kgBB Kina HCl dalam 100-200

cc cairan dekstrose 5% atau NaCl 0,9% selama 4 jam, cc cairan dekstrose 5% atau NaCl 0,9% selama 4 jam, - dilanjutkan dengan - dilanjutkan dengan 10 mg /KgBB dilarutkan dalam 10 mg /KgBB dilarutkan dalam

200 cc dekstrose 5% diberikan dalam waktu 4 jam 200 cc dekstrose 5% diberikan dalam waktu 4 jam -selanjutnya diberikan -selanjutnya diberikan dosis yang sama setiap 8 jam dosis yang sama setiap 8 jam --Apabila penderita sudah sadar, kina R/ peroral dgn Apabila penderita sudah sadar, kina R/ peroral dgn

dosis 3 x 300-600 mg selama 7 hari dihitung dari hari dosis 3 x 300-600 mg selama 7 hari dihitung dari hari I dosis parenteral.I dosis parenteral.

Dosis

i.v.i.v. 2,4 mg/kg BB pada jam 0, dan jam 12, 2,4 mg/kg BB pada jam 0, dan jam 12, kemudian dilanjutkan jam 24, 48 dst sampai 7 kemudian dilanjutkan jam 24, 48 dst sampai 7 hari. Dosis total 17 – 18 mg/ 7 hari ( 1 Amp= hari. Dosis total 17 – 18 mg/ 7 hari ( 1 Amp= 60 mg) atau 60 mg) atau

IVIV: 2,4/kgBB: 2,4/kgBB1,2 1,2 1,2 1,2 , 1,2 , 1,2 ,1,2/kgBB/24 jam ,1,2/kgBB/24 jam

3.23.2 mg/kg mg/kg IMIM pada hari I dibagi 2 dosis, pada hari I dibagi 2 dosis, dilanjutkan 1.6 mg/kg/ hari. dilanjutkan 1.6 mg/kg/ hari. TIDAK ivTIDAK iv (1 amp = (1 amp = 80 mg)80 mg)

SuppositoriesSuppositories, 1, 10 mg/kg at 0 & 4 hr followed by 0 mg/kg at 0 & 4 hr followed by 7 mg/kg at 24,36,48 & 60 hrs.7 mg/kg at 24,36,48 & 60 hrs.

ARTEMETER

DRUGS SIDE EFFECTS

ARTEMISININ

ARTESUNATE

Neurotoxicity in animal not human

WHO 2006 : AS is the recommended FIRST CHOICE in area low transmission

RECOMMENDED DOSES OF ANTI MALARIAL RECOMMENDED DOSES OF ANTI MALARIAL DRUGS FOR TREATMENT OF SEVERE MALARIADRUGS FOR TREATMENT OF SEVERE MALARIA

DRUGS DosisARTESUNATE

IV 2,4 mg/kg BB pada jam 0, dan jam 12, kemudian dilanjutkan jam 24, 48 dst sampai 7 hari. Dosis total 17 – 18 mg/ 7 hari ( 1 Amp= 60 mg)

atau IV: 2,4/kgBB1,2 1,2 , 1,2

,1,2/ kgBB/ 24 jam ARTEMETER 3.2 mg/kg IM pada hari I dibagi 2

dosis, dilanjutkan 1.6 mg/kg/ hari. TIDAK IV (1 amp = 80 mg)

ARTEMISININ Suppositories, 10 mg/kg at 0 & 4 hr followed by 7 mg/kg at 24,36,48 & 60 hrs.

Neurotoxaicity in animal not human

DOSIS ARTEMISININ PADA MALARIA BERATDOSIS ARTEMISININ PADA MALARIA BERAT

0 JAM 12.J 24.J 48.J 72.J Max 7 hari

2.4 Mg/KgBB

2.4 Mg/KgBB

2.4 Mg/KgBB

2.4 Mg/KgBB

2.4 Mg/KgBB

ARTESUNATE I.V/ I.M

* ARTEMETER , hanya I.M , dosis 1,6 mg/kg BB

ARTESUNATEI.V / I.M

1 Fl = 60 mg

ARTEMETHER I.M1 Amp = 80mg

Arthemeter-Lumefantrine vs Arthemeter-Lumefantrine vs Artesunate + AmodiaquineArtesunate + Amodiaquine

295 children > 5 years, Burundi, 14 295 children > 5 years, Burundi, 14 days :days :– ACPR : 99.3% (140/141), 95% CI:97.9-ACPR : 99.3% (140/141), 95% CI:97.9-

100% with AL vs 95.3% (142/149); 95% 100% with AL vs 95.3% (142/149); 95% CI: 91.9-98.7% with AS + AmoCI: 91.9-98.7% with AS + Amo

– Adverse events : vomiting on D1 1.5% Adverse events : vomiting on D1 1.5% AL vs 13% AS+Amo; on D2 : 1%AL vs AL vs 13% AS+Amo; on D2 : 1%AL vs 5% AS+Amo5% AS+Amo

Pengobatan malariaPengobatan malaria– Pengobatan malaria tanpa komplikasiPengobatan malaria tanpa komplikasi

Malaria Malaria falsiparumfalsiparum– Lini pertama:Lini pertama:– Artesunat+Amodiaquin+PrimakuinArtesunat+Amodiaquin+Primakuin

Dosis: diberikan selama tiga hariDosis: diberikan selama tiga hari Hari I:Hari I:

– Artesunat: 4 tablet + Amodiakuin 4 tablet + Artesunat: 4 tablet + Amodiakuin 4 tablet + Primakin 3 tabletPrimakin 3 tablet

Hari II:Hari II:– Artesunat: 4 tablet + Amodiakuin 4 tabletArtesunat: 4 tablet + Amodiakuin 4 tablet

Hari III:Hari III:– Artesunat: 4 tablet + Amodiakuin 4 tabletArtesunat: 4 tablet + Amodiakuin 4 tablet

Pengobatan malaria tanpa komplikasiPengobatan malaria tanpa komplikasiP. falciparumP. falciparum

Lini pertama:Lini pertama: Artesunat+Amodiaquin+PrimakuinArtesunat+Amodiaquin+Primakuin

HARI I Artesunat: 4 tablet + Amodiakuin 4 tablet + Primakin 3 tablet

HARI 2 4 tablet + Amodiakuin 4 tablet

HARI 3 4 tablet + Amodiakuin 4 tablet

Terapi malaria lini pertamaTerapi malaria lini pertamaHari Jeniss obat ≥ 15tahun/Tab

I Artesunat 4Amodiakuin 4Primakuin 2-3

2 Artesunat 4Amodiaquin 4

3 Artesunat 4Amodiakuin 4

SECOND LINE: severe malariaSECOND LINE: severe malariaLokasi Drugs/Dosis

Hospitalized patient

Quinine HCl 25 % in NaCl 0,9 % or Dextrosa 5 % per infusion, Dosage: 10 mg/KbBW/4 hour every 8 hours.Total dosage Quinine 30 mg/KgBW/24 hours

Patient in the field

Quinine HCl 25 % in NaCl 0,9 % or Dextrose 5 % intra muscular/IM: Dosage:10 mg/KbBW/4 hour every 8 hours.Total dosage qunine 30 mg/Kg BW/24 hours

If able to drink

follows by Quinine tab. + Doxy/ tetra capsule 7 days.

Pengobatan Pengobatan lini kedualini kedua bila terjadi bila terjadi rekrudensis atau justeru parasit rekrudensis atau justeru parasit

menetap (persisten)menetap (persisten)

Kina + doksisiklin Kina + doksisiklin 7 hari7 hari

atau atau

Tetrasiklin + primakuinTetrasiklin + primakuin

Derivat tetrasiklin

• Obat antibiotik yang bersifat sebagai anti malaria • Bersifat sebagai skizontosida jaringan P. falcifarum dan skizontosida darah untuk semua jenis plasmodium manusia

PrimakuinPelengkap pengobatan radikal P. falciparum u/ mencegah terjadinya penularan

PROGNOSISPROGNOSIS

UNCOMPLICATED & WITH PROMPT ANTIMALARIAL THERAPY GOOD

P. FALCIPARUM INFECTIONS WITH SEVERE COMPLICATIONS POOR

MORTALITYMORTALITY 0.1% case fatality rate provided 0.1% case fatality rate provided

prompt and effective treatmentprompt and effective treatment Ineffective, delayed Ineffective, delayed severe severe

malariamalaria Severe malaria, mortality Severe malaria, mortality 15 – 20 %15 – 20 % Untreated severe malaria, almost Untreated severe malaria, almost

always always fatalfatal / infaust / infaust

DOSIS

RECOMMENDED DOSES OF ANTI MALARIAL DRUGS RECOMMENDED DOSES OF ANTI MALARIAL DRUGS FOR TREATMENT OF SEVERE/CEREBRAL MALARIA FOR TREATMENT OF SEVERE/CEREBRAL MALARIA

XXXXXX

Hypoglycemia, Hypoglycemia, chinchonism, chinchonism, tinnitus, hearing tinnitus, hearing impairment, nausea, impairment, nausea, dysphoria, vomiting, dysphoria, vomiting, prolonged QT prolonged QT interval, interval, dysrhythmias, dysrhythmias, hypotensionhypotension

20 mg of dihydrochloride salt/kg by iv 20 mg of dihydrochloride salt/kg by iv infusion over 4 hr, then after infusion over 4 hr, then after loading, followed by 10 mg/kg over loading, followed by 10 mg/kg over 4 hr every 8 hr. Patients should not 4 hr every 8 hr. Patients should not received quinine or mefloquine received quinine or mefloquine within last 24 hrwithin last 24 hr

Alternatively, 7 mg of salt/kg can be Alternatively, 7 mg of salt/kg can be infused over a period of 30 min, infused over a period of 30 min, followed by 10 mg salt/kg over a followed by 10 mg salt/kg over a period of 4 hr, orperiod of 4 hr, or

10 mg of salt/kg (500 mg for adult) by 10 mg of salt/kg (500 mg for adult) by i.v infusion over 8 hr continously 3 i.v infusion over 8 hr continously 3 x a dayx a day

QuinineQuinine

DRUGSDRUGS SIDE EFFECTSSIDE EFFECTS

Pengobatan Pengobatan lanjutanlanjutan

Setelah pasien sadar/KU membaik, tx. Awal Setelah pasien sadar/KU membaik, tx. Awal parenteral dapat diubah dgn. Tx. Oralparenteral dapat diubah dgn. Tx. Oral

Diteruskan dengan :Diteruskan dengan : ACT dosis lengkap (selama 3 hari): AL , AS + AQACT dosis lengkap (selama 3 hari): AL , AS + AQ Artesunate/artemether tab. (total 7 hari ) + Artesunate/artemether tab. (total 7 hari ) +

doksisiklin 3-5 Kg BB 1 kali sehari selama 7 haridoksisiklin 3-5 Kg BB 1 kali sehari selama 7 hari Kina tab.(total 7 hari) + doksisiklin 7 hariKina tab.(total 7 hari) + doksisiklin 7 hari Bagi Bagi bumilbumil, anak-anak : doksisiklin diganti , anak-anak : doksisiklin diganti

dengan dengan klindamisin 10klindamisin 10 mg/Kg BB 2 kali sehari mg/Kg BB 2 kali sehari

Artemisinin-base Combination Artemisinin-base Combination Therapy (A.C.T)Therapy (A.C.T)

Rapid clerance parasitesRapid clerance parasites Rapid resolution of symptomsRapid resolution of symptoms Reduce parasites rapidlyReduce parasites rapidly

Recommendation WHO 2006 Recommendation WHO 2006 in using ACTs :in using ACTs :

Artemether-lumefantrineArtemether-lumefantrine Artesunate + amodiaquineArtesunate + amodiaquine Artesunate + mefloquineArtesunate + mefloquine Artesunate + sulfadoxine-Artesunate + sulfadoxine-

pyrimethamine/Fanidarpyrimethamine/Fanidar

ARTEMISININ FOR ARTEMISININ FOR SEVERE MALARIASEVERE MALARIA

Artesunate/ ARTS ( i.v./ i.m / Artesunate/ ARTS ( i.v./ i.m / supp)supp)

Artemether / ARTM (i.m.)Artemether / ARTM (i.m.) Arte-ether (i.m )Arte-ether (i.m ) Artemisinin ( supp )Artemisinin ( supp ) Dihydro-artemisinin ( supp )Dihydro-artemisinin ( supp ) Artelinate ( i.v)Artelinate ( i.v)

ANTI-BIOTICANTI-BIOTIC

DoxycyclinDoxycyclin TetrascyclineTetrascycline ClindamycinClindamycin AzithromycinAzithromycin

NEW ANTI MALARIA DRUGS - 2NEW ANTI MALARIA DRUGS - 2 ATOVAQUONEATOVAQUONE YINGHAOSUYINGHAOSU PIRONARIDINPIRONARIDIN ETAKUIN/ PIPERAKUINETAKUIN/ PIPERAKUIN BENFLUMETOL ( Lumefantrine )BENFLUMETOL ( Lumefantrine ) MEFLOQUINEMEFLOQUINE TAFENOQUINETAFENOQUINE SAMBILOTOSAMBILOTO

PENGOBATANPENGOBATAN

2. 2. Terapi SupresifTerapi Supresif Meringankan gejala Meringankan gejala KlorokinKlorokin

– Pendatang sementara ke daerah endermisPendatang sementara ke daerah endermis Klorokin : Klorokin : 300 Mg/Mgg300 Mg/Mgg 1 Mg 1 Mg selama di lokasi selama di lokasi 4 Mg 4 Mg

– Penduduk setempat dan penduduk baru yang Penduduk setempat dan penduduk baru yang akan menetapakan menetap Klorokin sekali/Mg Klorokin sekali/Mg 6 tahun atau 6 tahun atau Amodiakin 600 mg/2 mingguAmodiakin 600 mg/2 minggu

– Semua penderita demam di daerah endemis Semua penderita demam di daerah endemis Klorokin 600 mg, bila resistens Klorokin 600 mg, bila resistens Primakin 3 Primakin 3

tabtab Primakuin 1x1Primakuin 1x1

PENGOBATANPENGOBATAN Mepakrin 100 mg/hariMepakrin 100 mg/hari

– 2 Mg 2 Mg selama di lokasi selama di lokasi 4 mg 4 mg Pirimetamin (daraprim) 50 mingguPirimetamin (daraprim) 50 minggu

– 1 Mg 1 Mg selama di lokasi selama di lokasi 4 mg 4 mg Proguanil 100 mg/hr atau 300 mg/mingguProguanil 100 mg/hr atau 300 mg/minggu

– 1 Mg 1 Mg selama di lokasi selama di lokasi 4 Mg 4 Mg Kina satu tablet (250 mg)/hrKina satu tablet (250 mg)/hr

– 1 Mg 1 Mg selama di lokasi selama di lokasi 4 Mg 4 Mg Fansidar/suldox 1 tablet/mingguFansidar/suldox 1 tablet/minggu Doxycycline, 100 mg daily, 2 days before entering

the endemic area, while there, and for 4 weeks after leaving (this drug available in indonesia).(this drug available in indonesia).

Terima kasih, wassalam Terima kasih, wassalam

Merci GrazieDan

ke

Bedankt

Gracias

Hvala

Kiitos

TackObrigado

Ευχαριστω

Köszönöm

Teşekkür ederim

Спасібo

Syukron

Trimokaseh

ありがとう ごうざいますありがとう ごうざいます

Matur nuwun

Thank You

Nuhun pisan

Siesie

Kamsa hamnida

Kurru sumanga

Kukkun maMauli ate

Wassalam