malaria by siva

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Malaria:

Malaria Prepared & Presented by Dr. Siva Reddy Challa, Professor & HOD, Dept. of Pharmacology KVSR Siddhartha College of Pharmaceutical Sciences, Siddhartha Nagar, Vijayawada-520010 Andhra Pradesh, INDIA Email: sivareddypharma@gmail.com

MALARIA:

MALARIA Malaria is caused by a single-cell protozoa, the plasmodium. There are over 50 species of plasmodia but only 4 are infectious to humans: P. falciparum (most serious and lethal form) P. ovale (has dormant form in liver - relapse) P. vivax (has dormant form in liver - relapse) P. malariae

Severe P.falciparum malaria:

Severe P.falciparum malaria

Severe P.falciparum malaria:

Severe P.falciparum malaria

Malaria Blood Smear:

Malaria Blood Smear Remains the gold standard for diagnosis Giemsa stain distinguishes between species and life cycle stages parasitemia is quantifiable Threshold of detection thin film: 100 parasites/ l thick film: 5 -20 parasites/l Requirements: equipment, training, reagents, supervision Simple, inexpensive yet labor-intensive Accuracy depends on laboratorian skill

Interpreting Thick and Thin Films:

Interpreting Thick and Thin Films THICK FILM lysed RBCs larger volume 0.25 μl blood/100 fields blood elements more concentrated good screening test positive or negative parasite density more difficult to diagnose species THIN FILM fixed RBCs, single layer smaller volume 0.005 μl blood/100 fields good species differentiation requires more time to read low density infections can be missed

Malaria Blood Smear:

Malaria Blood Smear Prepare smears as soon as possible after collecting venous blood to avoid Changes in parasite morphology Staining characteristics Take care to avoid fixing the thick smear Risk of fixing thick when thin is fixed with methanol if both smears on same slide Let alcohol on finger dry to avoid fixing thick Be careful if drying with heat

Differentiation of falciparum:

Differentiation of falciparum P.falciparum trophozite P.vivax trophozite

Differentiation of falciparum:

Differentiation of falciparum P.falciparum shizont P.vivax shizont

Differentiation of falciparum:

Differentiation of falciparum P.falciparum gametocyte P.vivax gametocyte

Falciparum gametocytes:

Falciparum gametocytes Male Female

Electron Micrographs:

Electron Micrographs P.falciparum EM P.vivax EM

Life cycle of Plasmodium:

Life cycle of Plasmodium

PowerPoint Presentation:

Sporozoites. Motile malaria parasites that are infective to humans, inoculated by a feeding female anopheline mosquito. The sporozoites invade hepatocytes. Hypnozoites. Persistent liver stages of P. vivax and P. ovale malaria that remain dormant in host hepatocytes for an interval (most often 3–45 weeks) before maturing to hepatic schizonts. These then burst and release merozoites, which infect red blood cells. Hypnozoites are the source of relapses. Schizonts. Mature malaria parasites in host liver cells (hepatic schizonts) or red blood cells (erythrocytic schizonts) that are undergoing nuclear division. This process is called schizogony. Merozoites. Parasites released into the host bloodstream when a hepatic or erythrocytic schizont bursts. These then invade the red blood cells. Gametocytes. Sexual stages of malaria parasites present in the host red blood cells. Trophozoites. Stage of development of the malaria parasites within host red blood cells from the ring stage and before nuclear division. Mature trophozoites contain visible malaria pigment.

Drug classification:

Drug classification Tissue Schizonticides  drugs that kills liver forms of parasite. Blood Schizonticides  drugs that kills parasite in RBC. Gametocides  those that kills gametocytes

ANTI MALARIAL DRUGS:

ANTI MALARIAL DRUGS CHLOROQUINE QUININE MEFLOQUINE BLOOD SCHIZONTICIDES PYRIMETHAMINE PROGUANIL PRIMAQUINE - TISSUE(LIVER) SCHIZONTICIDE

Treatment of malaria:

Treatment of malaria Plasmodium spp Drugs Plasmodium falciparum If it is chloroquine senstive Chloroquine Plasmodium falciparum If it is chloroquine resistant ACT / Mefloquine/ Sulfadoxine and pyrimethamine Plasmodium malariae Chloroquine Plasmodium vivax Chloroquine +Primaquine Plasmodium ovale Chloroquine +Primaquine

PowerPoint Presentation:

23 Malaria Clinical Cure Radical Cure Clinical cure is achieved by prompt elimination of the parasite form responsible for the symptoms, that is, asexual erythrocytic form . Drugs used for Clinical cure are called Schizonticidal , or Suppressive agents . e.g., Chloroquine, Quinine/Quinidine, Mefloquine, Pyrimethamine Radical Cure implies the elimination of all parasite forms ( Exoerythrocytic (in Liver ) and the gametocytes ) from the body. This is achieved by Primaquine .

PowerPoint Presentation:

24 Malaria: Chemoprophylactic agents Chloroquine-sensitive P.falciparum, vivax, malariae, ovale Chloroquine-Resistant strains Chloroquine Mefloquine Atovaquone-proguanil Doxycycline Primaquine phosphate

PowerPoint Presentation:

25 Malaria: Treatment Chloroquine sensitive Chloroquine resistant or multidrug resistant Chloroquine Quinidine: IV for severe malaria Quinine Mefloquine Atovaquone-proguanil Artemisinin

Anti malarials:

Anti malarials Drug Mechanism of Action CHLOROQUINE Inhibition of polymerisation of Heme. MEFLOQUINE Unknown QUININE Unknown (may inhibits DNA synthesis) PRIMAQUINE Unknown

CHLOROQUINE:

CHLOROQUINE MECHANISM OF ACTION: 1.INHIBITS POLYMERISATION OF HEME TO HEMOZOIN BY INHIBITING POLYMERASE. HEME INHIBITS PROTIENASES. 2. ALKALANISATION OF FOOD VACUOLE. 3.INHIBITS DNA SYNTHESIS. MECHANISM OF RESISTANCE : EFLUX OF DRUG BY MEMBRANE ASSOCIATED P GLYCOPROTIEN.

CHLOROQUINE:

CHLOROQUINE INDICATIONS :1.MALARIA 2.RHEUMATOID ARTHRITIS 3.AMEBIC LIVER ABSCESS NOTE : IT KILLS 1.BLOOD SCHIZONTICIDES. 2.GAMETOCYTES (EXCEPT P.FALCIPARUM). NOT EFFECTIVE AGAINST LIVER STAGES.

CHLOROQUINE:

CHLOROQUINE A/E  Usually its well tolerated but 1.Pruritus is common (primarily in Africans). 2.Hemolysis in G6PD deficient persons. 3. Impaired hearing, confusion, psychosis , seizures 4. Agranulocytosis 5. Exfoliative dermatitis 6. Alopecia 7. Bleaching of hair 8. Hypotension 9. ECG changes [QRS widening, T wave abnormalities] 10 . Retinal deposits – Blindness

CHLOROQUINE:

CHLOROQUINE Contraindications : 1. Psoriasis & Porphyria (can cause acute attacks) Drug interactions: 1. Antidiarrheal agent Kaolin and Calcium and Magnesium containing antacids –-> decreases absorption of chloroquine . 2. Gold , Phenylbutazone (Along with chloroquine )–-> dermatitis.

QUININE:

QUININE P/K  Quinine is derived from the bark of the Cinchona tree from South America. Oral Use, Metabolized in liver and excreted in Urine. M(x) of A  Is Unknown! But, it is a blood Schizonticide against all four species. Gametocidal against P. Vivax and P. ovale but not P. Falciparum. It is not active against liver stage. May inhibits DNA synthesis.

Quinine:

Quinine . ADVERSE EFFECTS: 1. Tinnitus, headache, nausea, dizziness, flushing and visual disturbances -- CINCHONISM 2. Hypersensitivity reactions (skin rash, angioedema, urticaria, bronchospasm) 3. BLACK WATER FEVER : Hemolysis& Hemoglobinuria 4. Hemolysis in G6PD deficient patients 5. Intravenous infusions may cause thrombophlebitis 6 . Avoid in pregnancy

Quinine:

Quinine Drug interactions  1. Along with Mefloquine ( leads to cardiac failure) 2.Al containing antacids inhibits absorption of Quinine. 3.Quinidine Digoxin,Warfarin.

Mefloquine:

Mefloquine Indication : chloroquine resistant Falciparum malaria. Adverse effects : 1. GI distress 2., psychosis- Hallucinations . Headache ,dizziness, seizures 3 . Arrhythmias Contraindications : Arrhythmias,Psychosis Drug interactions : along with Quinine or Quinidine –-> cardiac arrest

PRIMAQUINE:

PRIMAQUINE INDICATION: Radical cure(killing liver dormant forms) of P. Vivax and P.Ovale ADVERSE EFFECTS: 1. GI distress 2. Hemolysis in G6PD deficiency patie nts 3. Avoid in pregnancy.

PowerPoint Presentation:

Drug Acute attack Eradication of liver stages Prophylaxis Chloroquine & hydroxychoroquine Yes No Yes (not in areas where falciparum is resistance) Mefloquine Yes No Yes (used for chloroqunine resistant falciparum) Quinine Yes No Yes(used for chloroquine resistant falciparum) Primaquine No Yes Yes (only for P. vivax or ovale)

PowerPoint Presentation:

Antimalarial drug Adverse effects Chloroquine/ Hydroxychloroquine GI distress Skin rash, pruritis [avoid in psoriasis] Headache, dizziness, ocular dysfunction( Retinal deposits ), psychosis hemolysis in G6PD deficiency. Mefloquine GI distress Headache ,dizziness, seizures ,psychosis arrythmias Quinine Cinchonism [ GI distress ,headache,vertigo,tinnitus] Hemolysis in G6PD deficiency patients Quinidine like cardiotoxic effects Avoid in pregnancy Primaquine GI distress Hemolysis in G6PD deficiency patients Avoid in pregnancy

PowerPoint Presentation:

Rx for malaria in pregnant woman – Atovaquone and Proguanil.

PowerPoint Presentation:

Therapeutics

Treatment Guidelines for uncomplicated P. falciparum malaria:

Treatment Guidelines for uncomplicated P. falciparum malaria the treatment of choice for uncomplicated falciparum malaria is a combination of two or more antimalarial medicines with different mechanisms of action. ACTs (Artesunate combination therapy) are the recommended treatments for uncomplicated falciparum malaria. the artemisinin derivative components of the combination must be given for at least three days for an optimum effect. the following acts are recommended: artemether plus lumefantrine, artesunate plus amodiaquine, artesunate plus mefloquine, artesunate plus sulfadoxine-pyrimethamine, and dihydrortemisinin plus piperaquine.

PowerPoint Presentation:

Treatment Guidelines for uncomplicated P. falciparum malaria Fixed-dose combinations are highly preferable to the loose individual medicines co-blistered or co-dispensed. The choice of ACT in a country or region will be based on the level of resistance of the partner medicine in the combination: • in areas of multidrug resistance (east Asia), artesunate plus mefloquine, or artemether plus lumefantrine or dihydroartemisinin plus piperaquine are recommended; and • in other areas without multidrug resistance (mainly Africa), any of the ACTs including those containing amodiaquine or sulfadoxine-pyrimethamine may still be effective.

PowerPoint Presentation:

 artemisinin and its derivatives should not be used as monotherapy.  second-line antimalarial treatment: • alternative ACT known to be effective in the region; • artesunate plus tetracycline or doxycycline or clindamycin, any of these combinations should be given for 7 days; • quinine plus tetracycline or doxycycline or clindamycin, any of these combinations should be given for 7 days. Treatment Guidelines for uncomplicated P. falciparum malaria

Treatment of Chloroquine sensitive acute malaria :

Treatment of Chloroquine sensitive acute malaria In patients who can take orally Choloroquine 600mg followed 12hours later by 300mg on day one. 300mg once daily on days two or three. ( OR) Amodiaquine 600mg followed by 200mg on day one; 400mg once a day on on days two and three Quinine 300mg tablets, 6 tablets daily for three days followed by 4 tablets daily for the next 10 days In patients, who can not take orally Chloroquine IM 2.5mg/kg every 4 hours or 3.5mg/kg every 6 hours (total dose does not exceed 25mg/kg base). Chloroquine IV 10mg/kg over 4 hours, followed by 5mg/kg base (given in a 2hour infusion) every 12 hours (total dose not to exceed 25mg/kg base).

Treatment of Chloroquine resistance malaria :

Treatment of Chloroquine resistance malaria In patients who can take orally Pyremethamine-sulfadoxine 3 tablets (single dose) followed by quinine 600mg orally three times a day for 2 days. (OR) Quinine 600mg three times a day together with doxycycline 100mg bid for 7 days (OR) Mefloquine 750mg orally , repeated after 6 hours (OR) Atovaquone 250mg + Proguanil 100mg combination , 4 tablets (single dose) daily for 3 consecutive doses . (OR) Sodium artesunate : 100mg orally 12 hourly on day one, then 50mg 12 hourly for 4 days

Treatment of Chloroquine resistance malaria :

Treatment of Chloroquine resistance malaria In patients who can not take orally Quinine hydrochloride by IV infusion : 20mg/kg in 500ml of dextrose sailne in 4 hours followed by 10mg/kg in dextrose saline over 2 hours , every 8 hours, until the patient is able to swallow. Then , oral quinine 600mg tid for 7 days and tetracycline 250mg 6 hourly IM for 7 days (OR) Artemether or arteether IM

PowerPoint Presentation:

Currently used antimalarial combinations for MDR falciparum malaria Artesunate + SP/Mefloquine/ Amodiaquone * Artemether + Lumefantrin * SP+ Chloroquine/ amodaiquone /quinine/ mefloquine Quinine + tetracycline/ Clindamycin Atovaquone + Proguanil Cloroproguanil + Dapsone Sulfadoxine + Pyerimethamine --------------------------------------------------------------------------- Only combinations to which resistance has not been reported. Note: SP is always given as a single dose. All other drugs are given for 7 days except quinine + tetracycline combination which is given for 7 days.

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