Diagnosis & Treatment of Malaria

Didi Candradikusuma

Malaria
40% of worlds population is at risk 300 - 500 million cases per year 1.5 to 2.0 million deaths per year (most of these are children under 6 years old in Africa)

400 Gigitan Nyamuk

200 Menginfeksi Manusia

100 Malaria Klinis

2 6% Malaria Berat

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) )

Plasmodium knowlesi (the fifth human plasmodium)

Natural host : Macaca fascicularis / Macaca nemestrina First reported in 2004 from Serawak, Malaysia Morphology similar to P. malariae Diagnosis by PCR No hipnozoite Fever every 24 hours, diarrhea, abdominal pain Can cause severe Malaria

Patogenesis Malaria

Malaria Life Cycle

Oocyst
Sporozoites

Zygote

Mosquito Salivary Gland

Gametocytes

Exoerythrocytic (hepatic) cycle

Hypnozoites

Erythrocytic Cycle

Malaria life cycle

Sex and sporogony in the mosquito Extraerythrocytic schizogony in the liver Merogony in the blood phase Gamogony in the blood and mosquito gut

SIKLUS HIDUP

Pathogenesis of Severe Malaria

Parasitemia

RBC Destruction

Parasite Sequestration

Immune Response

Microvascular Obstruction

Cytokines Release

Tissue Ischaemia, Hypoxia

Local & Systemic Inflammation

Complications / Dysfunction of Vital Organs

Pathogenesis of cerebral malaria

High cytokine levels could be toxic on their own High levels of cytokine also enhance the second process thought to be responsible for cerebral malaria: sequestration of infected RBCs

Sequestration & cytoadherence

The second model suggests sequestration is the main culprit In falciparum infections only early stages (rings) are found in the peripheral blood Trophozoites and schizonts are sequestered to the post-capilary venules by attachment to the endothelium

Ring stages

Trophopzoites & schizonts

Sequestration & cytoadherence

Cytoadherence correlates with pathogenesis (but high cytokine levels induce expression of endothelial adhesins enhancing attachment) Infected RBCs will adhere to the endothelium as well as to each other

Sequestration & cytoadherence

Rosetting (adhesion of infected RBCs to other RBCs) and clumping (adhesion between infected cells) was first observed in in vitro culture Rosetting was also found in 50% of field isolates and correlated strongly with the severity of the observed disease

Sequestration & cytoadherence

PfEMP1 (P. falciparum erythrocyte membrane protein) is found in knobs and is responsible for cytoadherence and rosetting PfEMP1 is a large membrane protein anchored in the RBC membrane with the bulk extending into the blood stream Two conserved binding domains and a series of highly variable domains

Malaria the disease

Asimtomatik Acut Malaria, uncomplicated Severe Malaria

WHO-TDR

Malaria the disease

9-14 day incubation period Fever, chills, headache, back and joint pain Gastrointestinal symptoms (nausea, vomiting, etc.)

Malaria the disease

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

Clinical Features

Malaria the disease

Malaria tertiana: 48h between fevers (P. vivax and ovale) Malaria quartana: 72h between fevers (P. malariae) Malaria tropica: irregular high fever (P. falciparum)

Malaria the disease

Symptoms intensify Irregular high fever Anxiety, delirium and other mental problems Sweating, increased pulse rate, severe exhaustion Worsening GI symptoms Enlarged spleen and liver

Malaria the disease

Incubation Period
Plasmodium falciparum Plasmodium vivax Plasmodium ovale Plasmodium malariae Plasmodium knowlesi 9 14 days 12 17 days 12 mo 16 18 days 18 40 days 9 12 days

Types of Infections
Recrudescence
exacerbation of persistent undetectable parasitemia, due to survival of erythrocytic forms, no exo-erythrocytic cycle (P.f., P.m.)

Relapse
reactivation of hypnozoites forms of parasite in liver, separate from previous infection with same species (P.v. and P.o.)

Recurrence or reinfection
exo-erythrocytic forms infect erythrocytes, separate from previous infection (all species)

Can not always differentiate recrudescence from reinfection

Clinical presentation
Varies in severity and course Parasite factors
Species and strain of parasite Geographic origin of parasite Size of inoculum of parasite

Host factors
Age Immune status General health condition and nutritional status Chemoprophylaxis or chemotherapy use

Mode of transmission
Mosquito Bloodborne, no hepatic phase (transplacental, needlestick, transfusion, organ donation/transplant)

Severity of disease and host factors

In addition to parasite factors, several host factors determine the outcome of exposure to malaria: Naturally-acquired immunity. People who are constantly exposed to malaria gradually acquire immunity, firstly against clinical disease and later against parasite infection. Clinical manifestations of malaria are most severe in the non-immune. In holoendemic areas, these are children aged <5 years and pregnant women (especially primagravidae). People of any age from areas that are free from malaria, or have limited malaria transmission, are at risk when they are exposed to malaria.

Red cell and haemoglobin variants. Well known examples of inherited factors that protect against malaria are Haemoglobin S carrier state, the thalassaemias and Glucose-6-phosphate dehydrogenase (G6PD) deficiency. Malaria provides the best known example whereby an environmental factor (malaria) has selected human genes because of their survival advantage.
Foetal haemoglobin (HbF): High levels of HbF occur in neonates, and in some people with inherited haemoglobin variants, protect against severe forms of P. falciparum malaria. Duffy blood group: P. vivax requires the Duffy blood receptor to enter red blood cells. Therefore, people who do not carry the Duffy blood group are resistant to this malaria species. This explains the rarity of P. vivax in Africa, as most Africans are Duffy blood group negative.

Other features of simple, uncomplicated malaria include:

o o o o o Vomiting Diarrhoea more commonly seen in young children and, when vomiting also occurs, may be misdiagnosed as viral gastroenteritis Convulsions commonly seen in young children. Malaria is the leading cause of convulsions with fever in African children. Pallor resulting mainly from the lysis of red blood cells. Malaria also reduces the synthesis of red blood cells in the bone marrow. Jaundice mainly due to haemolysis.

Malaria is a multisystem disease. Other common clinical features are: o Anorexia o Cough o Headache o Malaise o Muscle aches o Splenomegaly o Tender hepatomegaly

These clinical features occur in mild malaria. However, the infection requires urgent diagnosis and management to prevent progression to severe disease.

Severe and complicated malaria

Nearly all severe disease and the estimated >1 million deaths from malaria are due to P. falciparum. Although severe malaria is both preventable and treatable, it is frequently a fatal disease. The following are 8 important severe manifestations of malaria:

1. 2. 3. 4.

Cerebral malaria Severe malaria anaemia Hypoglycaemia Metabolic acidosis

5. Acute renal failure 6. Pulmonary oedema 7. Circulatory collapse, shock or algid malaria 8. Blackwater fever

Note: It is common for an individual patient to have more than one severe manifestation of malaria!

SEVERE MALARIA
DEFINITION: Patients with Plasmodium asexual parasitemia, with one or more CLINICAL or LABORATORY FEATURES :
-PROSTRATION -FAILURE TO FEED -IMPAIRED CONSCIUOUSNESS -RESPIRATORY DISTRESS -MULTIPLE CONVULSIONS, > 2X/24 Hours -CIRCULATORY COLLAPSE (Systolic < 70 , children < 50) -PULMONARY EDEMA (Radiology) -ABNORMAL BLEEDING (Spontaneous) -JAUNDICE + other vital organ dysfunction -HEMOGLOBINURIA
-SEVERE ANEMIA (5 GR% / 15%) -HYPOGLYCEMIA (< 40 MG/dL) -ACIDOSIS ( < 15 Mmol/L) -RENAL IMPAIRMENT ( > 3 mg% ) -HYPERLACTATEMIA ( > 5 mmol/L) -HYPERPARASITEMIA ( > 2% / 5% )

WHO, 2010

Plasmodium falciparum vivax knowlesi

Malaria Berat 26%

KEMATIAN 10 - 50 %

Plasmodium Infection in Pregnancy

Mother
Immune System

Fetus
Parasite Sequestration in Placenta

Tends to present as Severe Malaria

IUGR, IUFD, Fetal Distress, Low Birth Weight, Premature Labour (Congenital Malaria)

Faktor Predisposisi Malaria Berat

Anak usia Balita Wanita Hamil Immuno-compromized patients Penduduk daerah endemis yang lama meninggalkan daerah tersebut dan kembali mudik lagi Turis atau Wisatawan dari daerah Hipoendemis

Diagnosis
Malaria is a multisystem disease. It presents with a wide variety of non-specific clinical features: there are no pathognomonic symptoms or signs. Many patients have fever, general aches and pains and malaise and are initially misdiagnosed as having flu. P. falciparum malaria can be rapidly progressive and fatal. Prompt diagnosis saves lives and relies on astute clinical assessment: A good history Residence or a recent visit (in the preceding 3 months) to a malaria endemic area History of fever (may be paroxysmal in nature) Recognise significance of non-specific clinical features such as vomiting, diarrhoea, headache, malaise Physical examination Identify signs consistent with malaria: fever, pallor, jaundice, splenomegaly Exclude other possible causes of fever (e.g. signs of viral and bacterial infections)

The diagnosis of malaria should be considered in any unwell person who has been in a malarious area recently

Other methods of diagnosis of malaria

These are not routinely used in clinical practice. They include : a) Antigen capture kits. Uses a dipstick and a finger prick blood sample. Rapid test - results are available in 10-15 minutes. Expensive and sensitivity drops with decreasing parasitaemia. PCR based techniques. Detects DNA or mRNA sequences specific to Plasmodium. Sensitivity and specificity high but test is expensive, takes several hours and requires technical expertise. Fluorescent techniques. Relatively low specificity and sensitivity. Cannot identify the parasite species. Expensive and requires skilled personnel. Serologic tests. Based on immunofluorescence detection of antibodies against Plasmodium species. Useful for epidemiologic and not diagnostic purposes.

b)

c)

d)

Diagnosis
Clinical signs and symptoms Laboratory Examinations: - Blood smear (thick and thin blood film) - Rapid diagnostic test (immunochromatography) - QBC - PCR

MINISTRY OF HEALTH POLICIES

I. Diagnose must be confirm by microscope or Rapid Diagnostic Test II. Treatment: Artemisinin-based Combination Therapy (ACT). Stop Monotherapy ! III. Prevention: use LLIN, IRS, personal protections, etc.

CURRENT APPROACH MALARIA TREATMENT

Based on microscopic diagnosis Combination therapy Must radical treatment Outcome focus on clinical cure, parasitological clearance, and blocking transmission Monitoring therapeutic efficacy antimalarial drugs based on clinical and parasitological responses (in-vivo 28-42 days with or without ancillary measurements: drug blood level, genotyping, and strain analysis using molecular markers)

Mechanisms of action of anti malaria

Blood Schizonticides
chloroquine, quinine, SP,mefloquine mepaquine, halofantrine, artemisinin derivatives, piperaquine, atovaquone, pironaridine, tetracycline, doxycycline, clindamycine, azithromycine

Tissue Schizonticides
proguanil, primaquine, azithromycine, tetracycline

Sporontocides
SP, primaquine

Gametocides
primaquine (all species), quinine (vivax, malariae)

Combination Therapy
ACT : Artemisinin Combination Therapy Non ACT : (without artemisinin derivatives)

The ideal ACT combination

Resisten obat pasangan belum terjadi Pasangan obat mempunyai half-life panjang (> 4 hr) Artemisinin membunuh bentuk asexual dgn cepat; pasangan obat membersihkan parasit lainnya Ditolerensi baik, toksisitas rendah Artemisinin memiliki efek spectrum luas ( termasuk membunuh gametosit) Bila mungkin dosis tetap (Fixed dose ) Diproduksi secara standar Good Manufacturing Practice (GMP) Murah Supply obat cukup

Efek Samping Artemisinin

mild gastrointestinal disturbances, dizziness, tinnitus, reticulocytopenia, neutropenia, elevated liver enzyme values, electrocardiographic abnormalities, including bradycardia and prolongation of the QT interval, although most studies have not found any electrocardiographic abnormalities. The only potentially serious adverse effect : type 1 hypersensitivity reactions in approximately 1 in 3000 patients Neurotoxicity reported in animal studies, particularly with very high doses of intramuscular artemotil and artemether, but has not been substantiated in humans (3537). Evidence of death of embryos and morphological abnormalities in early pregnancy demonstrated in animal. Artemisinin has not been evaluated in the first trimester

Golongan ARTEMISININ
Artemisinin, Artesunate, Artemether, Arteether, DHA

Qinghaosu Sesquiterpene Lactone Larut dalam air dan diabsorbsi baik Efek bunuh parasit yang cepat Cepat dikonversi ke bahan aktif ( DHA) t1/2 in malaria: 2 hours Spektrum yang luas untuk semua jenis parasit dan staging Bila dipakai monotherapy, perlu 7 hari Direkomendasikan penggunaan ACT

Principles of malaria clinical management/uncomplicated malaria

Treatment of Uncomplicated Malaria

First line : Artemisinin Combination Therapy (ACT) Second line : non-ACT

Adjunct treatment of uncomplicated malaria

Fever
Acetominophen, paracetamol
Avoid aspirin in kids due to risk of Reyes Syndrome

Sponge baths

Anemia
Transfusion of RBCs may be needed Iron, folic acid

Rehydration
Solutions with extra glucose

Pengobatan Lini I, P. falsiparum menurut umur

Jenis obat Hari Dosis tunggal 1 Artesunate 01 bulan Jumlah tablet menurut kelompok umur 2 11 bulan 1-4 tahun 1 5-9 tahun 2 10 - 14 tahun 3 > 15 tahun 4

Amodiakuin
Primakuin

--

--

2
1

3
2

4
2-3

Artesunate Amodiakuin

1 1 1 1

2 2 2 2

3 3 3 3

4 4 4 4

Artesunate Amodiakuin

Atau
Dihydroartemisinin + piperaquin + Primakuin

Efektif

untuk Falciparum dan Vivaks

FDC Disiapkan untuk seluruh Indonesia

Pengobatan dengan Dihydroartemisinin-Piperakuin (DH-P)

Hari

Jenis obat

Jumlah tablet menurut kelompok umur (dosis tunggal) 0-1 bulan 2 11 bulan 14 tahun 59 tahun 10 14 tahun > 15 tahun

1--3 F, H1 V,H1 14

DHP Primakuin Primakuin

--

--

1,5 1

2 2

3-4 2-3 1

Dihydroartemisinin(DH) : 2-4 mg/kgBB (1tablet = 40 mg) Piperakuin phosphate(P): 16-32 mg/kgBB ( 1tablet = 320 mg) Primakuin : 0.25 mg 0.75 mg/kg BB

Treatment of Relapsing Malaria Vivax ACT 3 days Double-dose of primaquine for 14 days

Pengobatan Malaria Vivaks RELAPS

Jenis obat Hari Dosis tunggal 01 bulan Jumlah tablet menurut kelompok umur 2 11 bulan 1-4 tahun 5-9 tahun 10 - 14 tahun > 15 tahun

Artesunate
Amodiakuin Primakuin

- - --

- - --

1
1
1/2

2
2
1

3
3 11/2 3 3 11/2 3 3 1 1/2 1 1/2

4
4 2 4 4 2 4 4 2

Artesunate Amodiakuin Primakuin

1 1
1/2

2 2 1 2 2 1

Artesunate Amodiakuin Primakuin

1 1
1/2 1/2

4-14

Primakuin

Treatment Failure (WHO, 2003)

Early Treatment Failure
Parasitemia with severe clinical complication of malaria on day 1,2,3 Parasitemia on day 2 is greater than day 0 Parasitemia in day 3 (>25% from day 0) Parasitemia in day 3 shows positive result and axilla temperature > 37.5C

Late Treatment Failure

Late clinical and parasitological failure (LCF) : Parasitemia (the same species as day 0) with complication of severe malaria after day 3, t axilla > 37.5 C with parasitemia between day 428. Late parasitological failure (LPF) : Parasitemia is found (the same species with the day 0) on day 7-28 without increased axilla temperature (<37.5 oC).

Causes of Treatment Failure

Doctors - Misdiagnosis
- Late diagnosis - Late treatment - Inadequate dose

Patients - Come late

- Non compliant - Multiple complications

Parasite
- Resistant to drug

Management of Treatment Failure

Treatment failure within 14 days is very anusual Failure after 14 days : recrudenscence or reinfection Rescue treatment :
- Alternative ACT known effective in this region - Artesunat + tetracycline/doxycycline/clindamycine - Quinine + tetracycline/doxycycline/clindamycine

Pengobatan lini II alternatif kombinasi Kina + Doksisiklin/ Tetrasiklin/ Clindamycin (P. falciparum)
Hari Jenis obat Dosis tunggal 1 Kina Doksisiklin 0-11 bulan *) -Jumlah tablet menurut kelompok umur 1-4 tahun 3x -5- 9 tahun 3x1 -10 - 14 tahun 3x1 2 x 50 mg > 15 tahun 3 x (2-3) 2 x 100 mg

Primakuin
2-7 Kina Doksisiklin

*) --

3x --

1
3x1 --

2
3x1 2 x 50 mg

23
3x2 2 x 100 mg

Dosis TETRASIKLIN
Dosis CLINDAMYCIN

---

---

---

4x4 mg/kg BB
2x10 mg/kg BB

4 x 250 mg
2x10 mg/kg BB

Pengobatan multiresisten vivax/ ovale dengan kombinasi Kina + Doksisiklin/Tetrasiklin/Clindamycin (bila gagal pengobatan lini I)
Hari Jenis obat Dosis tunggal 1-7 Kina Doksisiklin 1 - 14 Primakuin 0 - 11 bulan *) ---Jumlah tablet menurut kelompok umur 1-4 tahun 3x - --5- 9 tahun 3x1 - --10 - 14 tahun 3x1 2 x 50 mg 4x4 mg/kg BB 2x10 mg/kg BB > 15 tahun 3 x (2-3) 2 x 100 mg 1 4 x 250 mg 2x10 mg/kg BB

Dosis TETRASIKLIN Dosis CLINDAMYCIN

PENYEBAB / ETIOLOGI
Plasmodium falciparum Mixed plasmodium ( Falciparum+ vivax) Plasmodium vivax Plasmodium knowlesi

PLASMODIUM KNOWLESI
Simian malaria ( Maccaca mullata) Unusual presentation P. Malariae Diagnosis by PCR Acute diare, abdominal pain, jaundice Algid malaria, hypotension Renal failure, respiratory failure

RECOMMENDED DOSES OF ANTI MALARIAL DRUGS FOR TREATMENT OF SEVERE MALARIA

DRUGS ARTESUNATE
i.v. 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) 3.2 mg/kg im pada hari I dibagi 2 Neurotoxicity in dosis, dilanjutkan 1.6 mg/kg/ hari. animal not human TIDAK iv (1 amp = 80 mg) Suppositories, 10 mg/kg at 0 & 4 hr followed by 7 mg/kg at 24,36,48 & 60 hrs.

Dosis

SIDE EFFECTS

Artemeter

Artemisinin

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

Dosis ARTEMISININ PADA MALARIA BERAT

48.J 0 JAM
2.4 Mg/ KgBB

12.J
2.4 Mg/ KgBB

24.J
2.4 Mg/ KgBB

48.J
2.4 Mg/ KgBB

72.J
2.4 Mg/ KgBB

Max 7 hari

ARTESUNATE I.V/ I.M

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

ARTESUNATE I.V / I.M

ARTEMETHER I.M
1 Amp = 80mg

1 Fl = 60 mg

Pengobatan Lanjutan
Setelah pasien sadar/KU membaik, tx. Awal parenteral dapat diubah dgn. Tx. Oral Diteruskan dengan : ACT dosis lengkap (selama 3 hari): AL , AS + AQ Artesunate/artemether tab. (total 7 hari ) + doksisiklin 3-5 Kg BB 1 kali sehari selama 7 hari Kina tab.(total 7 hari) + doksisiklin 7 hari Bagi bumil, anak-anak : doksisiklin diganti dengan klindamisin 10 mg/Kg BB 2 kali sehari

Pengobatan Pre-referral

Dianjurkan sebelum merujuk setidaknya dosis pertama obat antimalaria parenteral sudah diberikan. Obat yang dipilih : Artemether i.m. atau Artesunate i.m. Artesunate atau artemisinin supositoria Kina i.m. Kina i.v. (didampingi petugas medis ) ??

TREATMENT OF ORGAN FAILURE

ENCEPHALOPATHY/CONVULSION RENAL FAILURE ACIDOSIS HYPOGLYCAEMIA HYPERBILIRUBINAEMIA RESPIRATORY FAILURE HYPOTENSION SEPSIS SEVERE ANEMIA

CONVULSIONs
Uncommon in adults High flow oxygen and appropriate airway management Lorazepam i.v. (0.1 mg/kg) or Rectal/i.v. diazepam (0.5 mg/kg) If repeated doses are not effective loading Phenytoin (18 mg/kg over 20 minutes), or Phenobarbital (15-20 mg/kg over 10 minutes)

ACUTE KIDNEY INJURY (AKI)

Malaria related Acute Kidney Injury (MAKI) Penurunan fungsi ginjal dalam 48 jam : - Peningkatan serum kreatinin 0.3mg/dL atau - Peningkatan serum kreatinin 50% dari nilai dasar,atau - Penurunan urin output 0.5ml/kg/jam untuk 6 jam WHO : serum kreatinin > 3mg/dL Sering pada malaria dewasa dan jarang pada anak

Management of AKI
Appropriate Anti-Malaria Maintenance Fluid & Electrolytes Renal Replacement Therapy Treatment Complications Management of infections Avoid Nephrotoxic agent

Fluid & Diuretics

Oliguria/dehydrated : infusion of NS 20 ml/kgBW/60 minutes - auscultation, JVP observation/200ml - CVP monitoring (0 - +5) - No urine diuretic challenge Furosemide 40mg initially, no urine 100 mg. 200 mg, 400 mg every 30 minutes, no urine, dopamine 2.5 5 ug/kg/min (if no improved outcome)

Dialysis
Early dialysis improved survival Intermittent HD (daily/alternating) Continuous venovenous hemofiltration Continuous atriovenous hemofiltration Peritoneal Dialysis Less effective Indications : uremic symptoms, volume overload (pulmonary edema, congestive heart failure), pericardial rub, HCO3 < 15 mEq/L. K > 6.5 mEq/L

Adequacy of Dialysis
Dialysis is considered adequate when the post dialysis creatinine and urea levels decrease to 50% or less of predialysis values

PULMONARY MANIFESTATION IN MALARIA

Historically : - Bronchitic - Pneumonic - Bronchopnemonic Acute Lung Injury (ALI) Acute Respiratory Distress Syndrome (ARDS)

ARDS
Occurs in P falciparum, P vivax, 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 initation treatment Clinical: acute onset dyspnea respiratory failure

Management of ARDS
PRINCIPLES : Early Diagnosis Rapid Rx Anti Malarial Assisted ventilation Consider aggravating factors : - Bacterial sepsis - Secreting obstructive airways - Pneumothorax

Management ALI/ARDS
ICU Supported : prevent nosocomial infection, GI bleed, thrombo-embolism; adequate nutritional enteral intake Monitoring Oxygen saturation Fluid: conservative (136 491 ml), CVP 8 12 cmH2O Adrenalin is best avoided, other vasopressor such as dopamine should be preferred

Management ALI/ARDS
Spontaneous ventilation : a face mask with a high O2 to deliver FIO2 of up to 0.5 to 0.6 FIO2 > 0.6, CPAP > 10 cmH2O mechanical ventilator

Acidosis in Malaria
The etiology is not well understood Increase production and impaired metabolism of lactate and ketoacidosis Contributive factors : fever, severe anaemia, hypovolemic, alteration rheological, end products of parasites, decrease elimination through hepatic blood flow, Reyes like syndrome Sodium bicarbonate failed to improve lactat acidosis

METABOLIC ACIDOSIS
Occur in Acute Renal Failure : - hypovolemic - shock - pulmonary edema - hyperparasitemia Management : - Dialysis - NaBic if pH < 7.15, beware of Na overload pulmonary edema

MALARIA DALAM KEHAMILAN DAERAH ENDEMIS MALARIA

Semua ibu hamil didaerah beresiko penularan malaria pada kunjungan pertama (K1) di Ante Natal Care dilakukan pemeriksaan laboratory (RDT atau mikroskopis). Pengobatan Pf Pv atau mix tanpa komplikasi:
pada ibu hamil usia < 3 bulan dengan Kina tablet. pada ibu hamil usia > 3 bulan dgn Artesunat+Amodiakuin tab atau DHP.
Ibu hamil tidak boleh diberikan Primakuin.

MALARIA DALAM KEHAMILAN DAERAH ENDEMIS MALARIA

Pengobatan malaria berat:

pada ibu hamil usia < 3 bulan dengan Kina per infus. pada ibu hamil usia > 3 bulan dengan Artesunate injeksi intra vena bila di RS atau Artemeter injeksi intra muscular bila di lapangan. Bila sudah dapat minum dilanjutkan tab Kina atau Artesunat+Amodiakuin tablet atau Dihydroartemisinin Piperaquin.

Pencegahan terhadap gigitan nyamuk diberikan kelambu berinsektisida.

Faktor Prognosis
Kecepatan Diagnosis dan Pengobatan - semakin cepat pengobatan semakin rendah mortalitas Kegagalan Fungsi Organ - semakin sedikit organ vital yang terlibat semakin baik prognosis Kepadatan Parasit - Prognosis buruk bila parasite count tinggi dan terdapat skizon pada darah tepi

Prognosis
INDIKATOR KLINIS o Derajad Kesadaran prognosis jelek o AKI + Edema prognosis jelek o Asidosis Berat prognosis jelek o Gagal Nafas prognosis jelek o Perdarahan mortalitas o Imun (Splenectomi, Steroid,dll.) prognosis jelek

New AntiMalarial Agent

Artemisone (semi synthetic derivative of arthemisinin) Febrifugine & analogues (extracts of dichroa febrifuge Lourl Chang San) Fosmidomycine (Streptomyces levendulae) Naphthyridine