Diagnosis Malaria Menurut DepkesA. AnamnesisKeluhan utama pada malaria adalah demam, menggigil, berkeringat dan dapat disertai sakit kepala, mual, muntah, diare dan nyeri otot atau pegal- pegal. Pada anamnesis juga perlu ditanyakan:1. riwayat berkunjung ke daerah endemik malaria; 2. riwayat tinggal di daerah endemik malaria; 3. riwayat sakit malaria/riwayat demam; 4. riwayat minum obat malaria satu bulan terakhir; 5. riwayat mendapat transfusi darahB. Pemeriksaan Fisik1. Demam (>37,5 oC aksila) 2. Konjungtiva atau telapak tangan pucat 3. Pembesaran limpa (splenomegali) 4. Pembesaran hati (hepatomegali) 5. Manifestasi malaria berat dapat berupa penurunan kesadaran, demam tinggi, konjungtiva pucat, telapak tangan pucat, dan ikterik, oliguria, urin berwarna coklat kehitaman (Black Water Fever ), kejang dan sangat lemah (prostration).Keterangan :penderita malaria berat harus segera dirujuk ke fasilitas pelayanan kesehatan yang memiliki sarana dan prasaranayang lebih lengkap untuk mendapatkan perawatan yang lebih lanjut.C. Pemeriksaan LaboratoriumUntuk mendapatkan kepastian diagnosis malaria harus dilakukan pemeriksaan sediaan darah:1. Mikroskop: gold standard.Membuat sediaan darah tebal dan tipis. Menentukan:a) Ada tidaknya parasit malaria (positif atau negatif);b) Spesies dan stadium Plasmodium; c) Kepadatan parasit;1) Semi Kuantitatif(-)=negatif (tidak ditemukan parasit dalam 100 LPB/lapangan pandang besar)(+)= positif 1 (ditemukan 1 10 parasit dalam 100 LPB)(++)= positif 2 (ditemukan 11 100 parasit dalam 100 LPB) (+++)= positif 3 (ditemukan 1 10 parasit dalam 1 LPB)(++++)= positif 4 (ditemukan >10 parasit dalam 1 LPB)

Adanya korelasi antara kepadatan parasit dengan mortalitas yaitu: - Kepadatan parasit < 100.000 /ul, maka mortalitas < 1 % - Kepadatan parasit > 100.000/ul, maka mortalitas > 1 % - Kepadatan parasit > 500.000/ul, maka mortalitas > 50 %2) Kuantitatif Jumlah parasit dihitung per mikro liter darah pada sediaan darah tebal (leukosit) atau sediaan darah tipis (eritrosit). Contoh : Jika dijumpai 1500 parasit per 200 lekosit, sedangkan jumlah lekosit 8.000/uL maka hitung parasit = 8.000/200 X 1500 parasit = 60.000 parasit/uL. Jika dijumpai 50 parasit per 1000 eritrosit = 5%. Jika jumlah eritrosit 4.500.000/uL maka hitung parasit = 4.500.000/1000 X 50 = 225.000 parasit/uL.Sediaan darah tebalSediaan darah tipis

+/-Konfirmasi stadium & spesies parasit (morfologi lebih jelas)

Jumlah spesies

2. Pemeriksaan dengan tes diagnostik cepat (Rapid Diagnostic Test/RDT) Mekanisme: deteksi antigen parasit malaria, metoda imunokromatografi. DIgunakan pada:1. unit gawat darurat, 2. terjadi KLB, 3. dan di daerah terpencil yang tidak tersedia fasilitas laboratorium mikroskopis. Saat ini yang digunakan oleh Program Pengendalian Malaria adalah yang dapat mengidentifikasi P. falcifarum dan non P. Falcifarum.ParaSight- F Test-use a specific antigen of P. falciparum (pfHRP-2) and present in the parasite throughout the erythrocytic cycle.OptiMAL-detects parasite lactate dehydrogenase (pLDH)-> distinguish P. vivax from P. falciparum

Kelemanahan RDT:-tidak dapat mengukur densitas parasit (secara kuantitatif)-dapat terjadi hasil positif palsu karena adanya antigen residual dan gametosit muda-biaya mahal

3. Polymerase Chain Reaction (PCR) dan Sequensing DNA-Membedakan antara re-infeksi dan rekrudensi pada P. falcifarum.-Identifikasi spesies Plasmodium yang jumlah parasitnya rendah atau di bawah batas ambang mikroskopis.-Membedakan antara parasit impor atau indigenous.Cara KonvensionalDeteksi antigen/ RNA

Morfologi & jumlah parasit dapat dilihat dan dihitung-> evaluasi pengobatanMorfologi & jumlah parasit tidak dapt dilihat/ dinilai -> tidak dapat evaluasi pengobatan

Jumlah parasit dibawah microscopic threshold-> tidak terlihatJumlh parasit sedikit-> positif (1-2 parasit/ul)

4. Selain pemeriksaan di atas, pada malaria berat pemeriksaan penunjang yang perlu dilakukan adalah: a. pengukuran hemoglobin dan hematokrit; b. penghitungan jumlah leukosit dan trombosit;c. kimia darah lain (gula darah, serum bilirubin, SGOT dan SGPT, alkali fosfatase, albumin/globulin, ureum, kreatinin, natrium dan kalium, analisis gas darah); dand. urinalisis

box 7.3dHa+ppQ is an act option for first-line treatment of uncomplicated P. falciparum malaria worldwide. Strong recommendation, high quality evidenceGraDE evaluation (see Annex 7, tables A7.3.1A7.3.3) In clinical trials directly comparing DHA+PPQ and the currently recommended ACTs, DHA+PPQ was at least as effective at treating uncomplicated P. falciparum malaria (as measured by PCR adjusted treatment failure) as:artesunate plus mefloquine in Asia (day 63, 3 trials, 1182 participants; RR 0.39, 95% CI 0.190.79; high quality evidence);artemether plus lumefantrine worldwide (day 42, 4 trials, 1492 participants; RR 0.42, 95% CI 0.260.67; high quality evidence);artesunate plus amodiaquine worldwide (day 28, 2 trials, 679 participants; RR 0.47, 95% CI 0.230.94; moderate quality evidence).Other considerationsAt the time of publication, no DHA+PPQ product has been prequalified by WHO or registered by any stringent medicine regulatory authority.

In summary, the ACT options now recommended for treatment of uncomplicated falciparum malaria in alphabetical order are:artemether plus lumefantrine, artesunate plus amodiaquine,artesunate plus mefloquine,artesunate plus sulfadoxine-pyrimethamine,7 dihydroartemisinin plus piperaquine.

second-line treatments are recommended, in order of preference: an alternative ACT known to be effective in the region, artesunate plus tetracycline or doxycycline or clindamycin (given for a total of 7 days), quinine plus tetracycline or doxycycline or clindamycin (given for a total of 7 days).

box 7.5 recommendations: treatment of uncomplicated falciparum malaria in pregnancyfirst trimester: Quinine plus clindamycina to be given for 7 days (artesunate plus clindamycin for 7 days is indicated if thistreatment fails). An ACT is indicated only if this is the only treatment immediately available, or if treatment with 7-dayquinine plus clindamycin fails, or if there is uncertainty about patient compliance with a 7-day treatment.second and third trimesters: ACTb known to be effective in the country/region or artesunate plus clindamycin to be given for 7 days orquinine plus clindamycin to be given for 7 days. Pharmacovigilance programmes need to be established to continually monitor safety of antimalarial medicines in all trimesters, including inadvertent exposures in the early first trimester.a.If clindamycin is unavailable or unaffordable, then the monotherapy should be given. b.With the exception of DHA+PPQ for which there is insufficient information in second and third trimesters of pregnancy to use as first-line therapy.Lactating womenThe amounts of antimalarials that enter breast milk and are consumed by the breastfeeding infant are relatively small. Tetracycline is contraindicated in breastfeeding mothers because of its potential effect on the infants bones and teeth. Primaquine should not be used in nursing women, unless the breastfed infant has been determined not to be G6PD-deficient.box 7.6 recommendation: treatment for lactating women with uncomplicated falciparum malarialactating women should receive the recommended antimalarial treatment (including acts), except for dapsone, primaquine and tetracycline.box 7.8recommendations: treatment for travellers returning to non-endemic countries with uncomplicated falciparumfor travellers returning to non-endemic countries with uncomplicated malaria:a atovaquone plus proguanil (15/6 mg/kg [adult dose 4 tablets] once a day for 3 days) artemether plus lumefantrine dihydroartemisinin plus piperaquine quinine plus doxycyclineb or clindamycinfor severe malaria: the antimalarial treatment in travellers is the same as shown in Section 8 travellers with severe malaria should be managed in an intensive care unita.Halofantrine is not recommended as first-line treatment for uncomplicated malaria because of cardiotoxicity. b. Doxycycline should not be used in children under 8 years of age.

table 8.1 immediate clinical management of severe manifestations and complications of P. falciparum malariamanifestation/complication-immediate managementacoma (cerebral malaria) Maintain airway, place patient on his or her side, exclude other treatable causes of coma (e.g. hypoglycaemia, bacterial meningitis); avoid harmful ancillary treatment, such as corticosteroids, heparin and adrenaline; intubate if necessary.Hyperpyrexia Administer tepid sponging, fanning, a cooling blanket and antipyretic drugs. Paracetamol is preferred over more nephrotoxic drugs (e.g. NSAIDsb).Convulsions Maintain airways; treat promptly with intravenous or rectal diazepam or intramuscular paraldehyde. Check blood glucose.Hypoglycaemia Check blood glucose, correct hypoglycaemia and maintain with glucose- containing infusion.severe anaemia Transfuse with screened fresh whole blood.acute pulmonary oedemac Prop patient up at an angle of 45, give oxygen, give a diuretic, stop intravenous fluids, intubate and add positive end-expiratory pressure/ continuous positive airway pressure in life-threatening hypoxaemia.acute renal failure Exclude pre-renal causes, check fluid balance and urinary sodium; if in established renal failure add haemofiltration or haemodialysis, or if unavailable, peritoneal dialysis.spontaneous bleeding and coagulopathy Transfuse with screened fresh whole blood (cryoprecipitate, fresh frozen plasma and platelets, if available); give vitamin K injection.Metabolic acidosis Exclude or treat hypoglycaemia, hypovolaemia and septicaemia. If severe, add haemofiltration or haemodialysis.Shock Suspect septicaemia, take blood for cultures; give parenteral broad-spectrum antimicrobials, correct haemodynamic disturbances.box 9.1in areas with chloroquine resistant P. vivax, artemisinin-based combination therapies (particularly with those whose partner medicines have long-half lives) are recommended for the treatment of P. vivax malaria. Weak recommendation, moderate quality evidenceGraDE evaluation (see Annex 9, tables A9.6.1 and A9.6.2) Two trials compared DHA+PPQ to alternative ACTs (AL6 and AS+AQ) in Indonesia where all groups were also given primaquine to clear the liver stage parasites. DHA+PPQ reduced the number of relapses by day 42 compared to AL (1 trial, 126 participants; RR 0.16, 95% CI 0.070.38; moderate quality evidence) and AS+AQ (1 trial, 84 participants; RR 0.16, 95% CI 0.050.49; moderate quality evidence). There are no trials comparing DHA+PPQ and AS+MQ in P. vivax mono-infection. At day 42, the patients in the DHA+PPQ groups were also less likely to be anaemic, although this data includes participants with P. falciparum mono-infection at baseline, and recurrence of P. falciparum was also lower with DHA+PPQ. This effect is likely to be a prophylactic effect related to the longer half-life of DHA+PPQ.Other considerationsThe panel noted the programmatic advantage of these ACTs also being highly effective against P. falciparum. This effect is likely to be a prophylactic effect related to the longer half-life of DHA+PPQ.box 9.2at least a 14-day course of primaquine is required for the radical treatment of P. vivax Strong recommendation, very low quality evidenceGraDE evaluation (see Annex 9, table A9.7.1) A 14-day course of primaquine significantly reduces the relapse rate of P. vivax compared to a 5-day course (2 trials, 186 participants; RR 0.1, 95% CI 0.030.35; low quality evidence).Other considerationsIn addition, in clinical trials, CQ plus 14 days of primaquine has been shown to be superior to CQ alone in reducing relapses (6 trials, 1071 participants; OR 0.24, 95% CI 0.12 0.45). No difference has been shown between CQ plus 5 days of primaquine and CQ alone (3 trials, 2104 participants).box 9.3 uncomplicated p. vivax malariachloroquine 25 mg base/kg body weight divided over 3 days, combined with primaquine 0.25 mg base/kg body weight, taken with food once daily for 14 days is the treatment of choice for chloroquine-sensitive infections. in oceania and south-east asia, the dose of primaquine should be 0.5 mg/kg body weight.acts combined with primaquine for chloroquine-resistant vivax malaria.in mild-to-moderate G6pd deficiency, primaquine 0.75 mg base/kg body weight should be given once a week for 8 weeks. in severe G6pd deficiency, primaquine is contraindicated and should not be used.Where act (exception as+sp) has been adopted as the first-line treatment for P. falciparum malaria, it may also be used for P. vivax malaria in combination with primaquine for radical cure. artesunate plus sulfadoxine-pyrimethamine is not effective against P. vivax in many places.

Patofisiologi Metabolic AcidosisThis has been considered to be mainly a lactic acidosis, although ketoacidosis (and sometimes salicylate intoxication) may predominate in children and the acidosis of renal failure is common in adults. Pathogenesis: lactatepyruvate ratios often exceed 30 reflecting tissue hypoxia and anaerobic glycolysis. -Lactic acidosis results from several discrete processes: 1.the tissue anaerobic glycolysis consequent upon microvascular obstruction impeded by adherence of infected erythrocytes to the endothelium of post-capillary venules and/or increased rigidity of uninfected cells-> reduce O2 delivery to tissuesa..Cytoadherence-> Rosetting-> Marked reductions in the deformability of uninfected RBCs-> compromises blood flowb. Dehydrated and hypovolemia can exacerbates microvascular obstruction by reducing perfusion pressurec. Destruction of RBCs and anemia further compromises oxygen delivery: digested host Hb: haemozoin (malaria pigment) containing leucocytes -> high level of proinflammatory cytokines (TNF-, IFN-, Interleukins, Th1) -> sequestration (contributing to microcirculatory obstruction) ->cellular dysfunction in endothelial cells, dendritic cells, monocytes/ macrophages -> provoke a metabolic shift within host cells to anaerobic glucose metabolism and increased lactic acid production; 2. a failure of hepatic and renal lactate clearance;3. and the production of lactate by the parasite (through direct stimulation of cytokines). Parasit matur konsumsi glukosa -> 90% konversi-> L+lactic acid (plasmodia tidak memiliki enzim untuk masuk citric acid cycle) -> Hyperlactataemia (associated with hypoglycaemia and is accompanied by hyperalaninaemia and elevated glycerol concentrations reflecting the impairment of gluconeogenesis through the Cori cycle).Triglyceride and free fatty acid levels are also elevated in acute malaria and plasma concentrations of ketone bodies are raised in patients who have been unable to eat. Ketoacidosis may be prominent in children. In severe malaria, there is dysfunction of all organ systems, particularly those with obligatory high metabolic rates. The endocrine glands are no exception. Pituitarythyroid axis abnormalities result in the sick euthyroid syndrome and also parathyroid dysfunction. Mild hypocalcaemia is common and hypophosphataemia may be profound in the very seriously ill. By contrast, the pituitaryadrenal axis appears normal in acute malaria. Management:1. Maintain airway patency & O2 delivery; unconsciuous, severe shock, unstable-> intubate2. IV line; tachycardia, hypotension, or other poor tissue perfusion-> replace adequate intravascular fluid volume3. Monitor cardiac dysrhytmias4. Sodium bicarbonate is controversial and generally should be avoidedHemoglobinuria results form severe intravascular hemolysis; usually seen in non-immune or semi-immune individuals -due to non-immune destruction of parasitized red cells in case of high parasitemia or immune mediated destruction of parasitized as well as non-parasitized red cells. G6DP Deficiency develop hemolysis when treated with oxidant drugs like primaquine Oocur rapidly, Hb drop significantly in few hours Urine is dark red to almost black, output slowly drops May be associated with severe anemia, ARF, peripheral circulatory failure Black water fever: increase Hb into the circulation Repeated exposure to quinine -> black water fever Occurs when the capacity of haptoglobinTreatment: Treatment is directed towards anemia and renal failure.Transfusion of whole blood or packed cells should be started if the hemoglobin level is less than 5g%.Renal failure can be treated conservatively by careful fluid-electrolyte management and use of diuretics like furoscemide. Dialysis must be considered in patients who do not respond to conservative treatment.Antimalarial therapy In cases with hemolysis following primaquine therapy, Glucose 6 phosphate dehydrogenase assay should be done and the drug should be stopped.

Pengendalian Vektor MalariaVektor: nyamuk Anopheles, dengan ciri khas menungging saat hinggap atau menghisap darah, mempunyai siklus hidup sempurna terdiri dari telur (1-2 hari), jentik (6-8 hari), kepompong (1-2 hari) dan nyamuk (2-3 bulan).tempat perkembangbiakan vektor malaria dibagi menjadi 2 tipe yaitu : Tipe permanen seperti: Rawa-rawa, laguna, sawah non teknis dengan aliran air gunung, Mata air, Kolam.1. Tipe temporer seperti: Muara sungai tertutup pasir di pantai, genangan air payau di pantai, kobakan air di dasar sungai waktu musim kemarau, genangan air hujan, sawah tadah MedicationsMalaria Prophylaxis-3-6 month temporary stay in malaria endemic areas1. Doxycicline 100 mg/ daily for P. falciparum, starting 1-2 days before departure to endemic areas, until 1-2 weeks after coming back2. or Mefloquine weeky for all parasites starting 2 weeks before departure to malaria endemic areas until 4 weeks after arrived.Health EducationPromoting awarenessFisikMenghasilkan keadaan tidak menguntungkan bagi nyamuk.-penimbunan kolam-pengangkatan tumbuhan air- pengeringan sawah secara berkala (2 minggu sekali)-pemasangan kawat kasa pada jendelaSecara kimiawi-penyemprotan rumah serta bangunanbangunan lainnya dengan menggunakan fenitrothion, Dichloro Diphenyl Trichloroethane (DDT) dan lain-lain.-Kelambu (Long Lasting Insecticide Treated Nets)-Indoor residual spray: DDT, pyerethroids cyfluthrin, deltamethrin-repellents: DEET (diethyl-meta-toluamide), icaridin-larvasidaBiologiMenggunakan beberapa agent biologis: predator pemakan jentik (clarviyorous fish) yaitu gambusia, guppy, ikan nila dan ikan kepala timah, patogen misalnya dengan virus yang bersifat cytoplasmic polyhedrosis, dengan bakteri seperti Bacillus thuringiensis subsp. dengan protozoa seperti Nosema vavraia dan dengan fungi seperti Coelomomyces (WHO, 1995; Sigit dan Hadi, 2006).Fauna yang bersifat sebagai predator jentik nyamuk menurut Bates (1970) adalah filum Rotifera, filum Annelida, filum Colenterata: Hydra, filum Mollusca: Limnea. Predator dari kelompok hewan vertebrata adalah Pisces, Amphibia, Reptilia dan Aves. Sedangkan predator dari filum Arthopoda meliputi 3 kelas yaitu kelas Crustasea contohnya Entomostraca dan udang, kelas Arachnida yaitu laba - laba, kelas insekta terdiri atas Ephemeroptera (lalat sehari), Odonata (capung), Hemiptera (kepik-kepik), Coleoptera (kumbang-kumbang) dan Diptera (sebangsa lalat). Tetapi predator yang paling penting adalah ikan pemakan jentik.