Malaria 2003

4,662 views

Published on

Published in: Health & Medicine, Technology
0 Comments
3 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
4,662
On SlideShare
0
From Embeds
0
Number of Embeds
228
Actions
Shares
0
Downloads
231
Comments
0
Likes
3
Embeds 0
No embeds

No notes for slide
  • Malaria 2003

    1. 2. Malaria <ul><li>Types </li></ul><ul><li>Lifecycle </li></ul><ul><li>Drugs-classification </li></ul><ul><li>Individual drugs </li></ul><ul><li>Dosage regimen </li></ul><ul><li>Chemo-prophylaxis </li></ul><ul><li>Newer anti-malarials </li></ul><ul><li>Vaccine </li></ul>
    2. 3. <ul><li>Devastating parasitic infection </li></ul><ul><li>Attacks-500 million </li></ul><ul><li>Mortality –2 million[1million children]. </li></ul><ul><li>Except N.America, Europe, Russia </li></ul>
    3. 4. Chloroquine resistant-PF Chloroquine sensitive-PF Malaria Endemic Areas Mexico, Central America west of Panama canal, Carribean, South America, middle east Resistant PV Indonesia,Papua New Guinea, Burma
    4. 5. <ul><li>Types </li></ul><ul><li>P.vivax - Benign tertian </li></ul><ul><li>P.Falciparum - Malignant tertian </li></ul><ul><li>P.ovale -Benign tertian </li></ul><ul><li>P.Malariae -Benign Quartan </li></ul>
    5. 6. Transmission <ul><li>“ Bite of Infected Female Anopheles Mosquito” </li></ul><ul><li>Blood transfusion </li></ul><ul><li>Congenital </li></ul><ul><li>Sharing needles </li></ul>
    6. 7. Life Cycle
    7. 8. Hepatic Stage <ul><li>P.F and P.M No persistent tissue phase </li></ul><ul><li> No Hypnozoites </li></ul><ul><li>No relapse </li></ul><ul><li>No Radical cure required </li></ul><ul><li>P.V and P.O.- Persistent tissue phase + </li></ul>
    8. 9. Erythrocytic Phase <ul><li>Most of the drugs act in this stage </li></ul><ul><li>Leads to clinical cure </li></ul><ul><li>Most of the drugs do not prevent transmission </li></ul><ul><li>Chemoprophylaxis </li></ul>
    9. 10. Why P.F. Serious? <ul><li>P.Palciparum </li></ul><ul><li>Produces </li></ul><ul><li>Leads to </li></ul><ul><li>Binds-RBCs all ages </li></ul><ul><li>Alters surface </li></ul><ul><li>Grows in low o2 </li></ul><ul><li>Micro-vascular blocks </li></ul><ul><li>Cytokine release </li></ul><ul><li>Endotoxin release </li></ul><ul><li>High parasitemia </li></ul><ul><li>Cerebral malaria </li></ul><ul><li>Hypoglycemia </li></ul><ul><li>Shock, Multi organ failure </li></ul><ul><li>Death </li></ul>
    10. 11. Classification of Drugs <ul><li>Cinchona alkaloids: Quinine & Quinidine </li></ul><ul><li>Quinolines: </li></ul><ul><li>1. 4-Aminoquinolines- Chloroquine </li></ul><ul><li> Hydroxychloroquine </li></ul><ul><li>Amodiaquine </li></ul><ul><li>Piperaquine </li></ul><ul><li>2. 8-Aminoquinolines- Primaquine </li></ul><ul><li>Tafloquine </li></ul><ul><li>Bulaquine </li></ul>
    11. 12. Classification…… <ul><li>Quinolines.. </li></ul><ul><li>3. Quinoline methane- Mefloquine </li></ul><ul><li> Halofentrine </li></ul><ul><li> Lumefantrene </li></ul><ul><li>Antifolates: </li></ul><ul><li>1. Biguanides- Proguanil </li></ul><ul><li>2. Diaminopyrimidine- Pyremethamine </li></ul><ul><li>3. Sulfonamides- Sulfadoxine </li></ul><ul><li> Dapsone </li></ul>
    12. 13. Classification…… <ul><li>Artemisinin compounds : Artesunate </li></ul><ul><li>Artemether </li></ul><ul><li>Arteether </li></ul><ul><li>AMA: Doxycycline, Clindamycin, </li></ul><ul><li>Others Atovaquone , Pyoronaridine </li></ul>
    13. 14. Spor Liver RBC forms Class I P.E Hypno Asex Gam Chloroquine - - - + ( ±) Mefloquine - - - + - Quinine - - - + ( ±) Pyrimethamine+ Sulfadoxin - ± - + _ T.C - - - ± - Class II Atovaquone+Proguanil - [+] - + - Class III Primaquine - + + - +
    14. 15. Lesson! <ul><li>No drug acts on Sporo </li></ul><ul><li>None very effective against both liver & RBC stages </li></ul><ul><li>True prevention not possible, only suppress symptomatic malaria. </li></ul><ul><li>Complete cure requires more than one drug </li></ul>
    15. 16. Clinical utility <ul><li>Class I: </li></ul><ul><li>Liver and sexual forms- No action. </li></ul><ul><li>Active against RBC stage Only </li></ul><ul><li>Hence- used in the tt and prevention of clinical malaria </li></ul><ul><li>Prophylaxis-Takes several weeks to exhaust liver stages </li></ul>
    16. 17. Clinical utility…… <ul><li>Class II: Act against early Liver & RBC forms, Reduces period of post exposure in prophylaxis </li></ul><ul><li>Class III: Unique! Radical cure, No place in Symptomatic treatment. </li></ul>
    17. 18. Use and Classification <ul><li>Causal prophylactics- </li></ul><ul><li>Target early liver forms </li></ul><ul><li>Eg.????????? </li></ul><ul><li>Terminal prophylaxis and radical cure- </li></ul><ul><li>Target hypnozoites </li></ul><ul><li>Eg.???????? </li></ul><ul><li>Suppressive prophylactics and clinical cure- </li></ul><ul><li>Target asexual RBC forms </li></ul><ul><li>Eg.????? </li></ul>
    18. 19. Life Cycle And Drugs NONE Pyrimethamine Proguanil Primaquine Most of the drugs Except Primaquine Chloroquine Quinine [not F.P.]
    19. 20. Quinine <ul><li>Holy bark, Cardinal’s bark, Jesuit’s </li></ul><ul><li>Quinine & Quinidine-Alkaloids from Cinchona bark. Cheapest source </li></ul><ul><li>H/O 350 yrs. </li></ul><ul><li>Even today d.o.c severe and resistant malaria </li></ul>
    20. 21. Quinine contd… <ul><li>Anti-malarial action : </li></ul><ul><li>Active against asexual erythrocytic forms </li></ul><ul><li>Against gametocytes of P.V & P.M(Not P.F.) </li></ul><ul><li>More toxic, less effective than chloroquine(If suceptible to both) </li></ul><ul><li>Chlo. & MDR strains respond. </li></ul><ul><li>Parenteral treatment </li></ul>
    21. 22. Quinine contd… <ul><li>Anti-malarial action ( M.O.A.) </li></ul><ul><li>Asexual parasites digest Hb in ACIDIC food vacuoles </li></ul><ul><li>Quinine(Alkaline) Concentrated in vacuoles </li></ul><ul><li>Raises pH ‘ALKALINE‘ </li></ul><ul><li>Free radicals and heme generated </li></ul><ul><li>These Toxic sub. sequestered by parasite as non toxic hemozoin </li></ul><ul><li>Prevents hemozoin formation </li></ul><ul><li>May also bind to heme- Toxic </li></ul>
    22. 23. Quinine contd… <ul><li>Chloroquine, </li></ul><ul><li>Amodiaquine, </li></ul><ul><li>Mefloquine, Lumefantrine </li></ul><ul><li>Halofantrine & Pyronaridine </li></ul><ul><li>Have similar MOA </li></ul>
    23. 24. Quinine contd… <ul><li>Skeletal muscles: Decreases contractile force & excitability </li></ul><ul><li>Antagonize physostigmine. </li></ul><ul><li>Myesthenia gravis? </li></ul><ul><li>Myotonia congenita? </li></ul><ul><li>Local-Inflammatory and anesthetic </li></ul><ul><li>Uterus-Stimulant </li></ul>
    24. 25. Quinine contd… <ul><li>PK: well absorbed from GIT, i.m. </li></ul><ul><li>Metabolized by CYP3A4 </li></ul><ul><li>Acidic urine ↑ excretion </li></ul><ul><li>α 1-acid glycoprotein in malaria protects from toxicity of high plasma concn.! </li></ul>
    25. 26. Therapeutic uses: <ul><li>Severe and resistant malaria </li></ul><ul><li>Nocturnal leg cramps </li></ul><ul><li>Spermicidal-Vaginal creams </li></ul><ul><li>Sclerosing agent-V.V. </li></ul><ul><li>Quinidine used as anti-arrhythmic </li></ul>
    26. 27. Quinine ….ADE <ul><li>Fatal dose 2-8g. </li></ul><ul><li>Cinchonism : Tinitus, high tone deafness, visual disturb., nausea, vomiting </li></ul><ul><li>Hypoglycemia </li></ul><ul><li>Cardiac: Arrhythmia, AV block, Hypotension more with quinidine </li></ul><ul><li>Blackwater fever : Hypersensitivity: </li></ul><ul><li>“ Hemolysis-hemoglobinemia -hemoglobinuria” Anuria Renal failure and death. </li></ul><ul><li>Purpura </li></ul>
    27. 28. Quinine ….Caution <ul><li>Hypersensitivity </li></ul><ul><li>Hemolysis- discontinued </li></ul><ul><li>Cardiac arrhythmia, tinitus, optic neuritis </li></ul><ul><li>Irritant </li></ul><ul><li>Fairly safe in pregnancy </li></ul>
    28. 29. Quinine (DI) <ul><li>Antacids </li></ul><ul><li>Reduces absorption of digoxin </li></ul><ul><li>Elevates plasma conc.of Warfarin </li></ul><ul><li>Enhances effect of NM blockers </li></ul><ul><li>Acidification of urine ↑ clearance </li></ul>
    29. 30. Chloroquine <ul><li>Anti-malarial spectrum: </li></ul><ul><li>Erythrocytic forms of all species, Gametocyte of all except P.F, </li></ul><ul><li>No activity against tissue forms </li></ul><ul><li>MOA: As before </li></ul><ul><li>Resistance: Resistant strains concentrate chloroquine less in vacuoles. </li></ul><ul><li>Crt-Chloroquine resistant transporter and Pfmdr transporters </li></ul>
    30. 31. Chloroquine contd… PK: <ul><li>Well absorbed by oral , s.c, i.m. </li></ul><ul><li>Extensively sequestrated in tissues-Large V (100L/k.g) </li></ul><ul><li>Loading dose is required-Wide dist. </li></ul><ul><li>Half life-1 week </li></ul><ul><li>Slow IV-slow dist. </li></ul><ul><li>Oral-PK of absorption and dist. matched </li></ul>
    31. 32. <ul><li>Clinical cure & Chemoprophy.(Sensitive strains) </li></ul><ul><li>Hepatic amoebiasis </li></ul><ul><li>RA </li></ul><ul><li>Discoid lupus,SLE </li></ul><ul><li>Lepra reaction, Sarcoidosis </li></ul><ul><li>Photosensitivity reaction </li></ul><ul><li>Porphyria cutanea tarda </li></ul><ul><li>Chikengunya? [HCQ] </li></ul>Chloroquine- Uses With other agents
    32. 33. Chloroquine contd… ADE: <ul><li>Remarkably safe in th. doses. Safety margin is narrow </li></ul><ul><li>Parenteral - Rapid infusion -> </li></ul><ul><li>Arrhythhmia, Hypotension, arrest. </li></ul><ul><li>More than 5g fatal </li></ul><ul><li>Oral - GIT, headache, VISUAL disturbances, blurring, rashes </li></ul>
    33. 34. Chloroquine contd… ADE : <ul><li>Chronic therapy : Accumulates in melanin rich tissues( ↑ 250mg/day) </li></ul><ul><li>Irreversible retinopathy, ototoxicity [Total cumulative dose of more than 1G/Kg] </li></ul><ul><li>Discolouration of nail bed& m.m., bleaching of hair </li></ul><ul><li>Myopathy, neuropathy, neuropschiatric, cardiopathy </li></ul><ul><li>Optho and Neuro exam PERIODICALLY </li></ul>
    34. 35. Chloroquine contd… ADE : <ul><li>Caution: </li></ul><ul><li>Not used with Mefloquine (Siezures) </li></ul><ul><li>Cautiously in liver disease renal failure, G6PD def </li></ul><ul><li>CI- Epilepsy, myesthenia gravis, </li></ul><ul><li>Opposes anticonvulsants, arrhythmogenic with halofentrine and amiodarone </li></ul>
    35. 36. Chloroquine contd… <ul><li>Preperations: </li></ul><ul><li>Tab, Syp, Injection </li></ul><ul><li>Oral- Chl.Po 4 ( 250mg salt=150 mg base) </li></ul><ul><li>Dose </li></ul><ul><li>Curative: </li></ul><ul><li>Prophylactic </li></ul>
    36. 37. Mefloquine <ul><li>Antimalarial action- Against blood schizonts </li></ul><ul><li>MOA : Exactly not known. Similar to chloroquine </li></ul><ul><li>PK : Slow oral absorption. Food ?. Excretion fecal </li></ul><ul><li>No parenteral (Local reaction) </li></ul><ul><li>t 1/2 -2-3 weeks –enterohepatic circulation </li></ul><ul><li>Uses : Prophy. & Tt of drug resistant malaria[With Artimisinin] </li></ul>
    37. 38. Mefloquine ADE contd… <ul><li>Vomiting( repeat if within 1 h.) </li></ul><ul><li>CNS- seizures, confusion or decreased sensorium, acute psychosis, and disabling vertigo.[reversible] </li></ul><ul><li>CI: Pregnancy(avoided for 3 mo. After stopping), Epilepsy, psychotics, pilots </li></ul><ul><li>H/O ADE to other quinolines </li></ul>
    38. 39. Mefloquine Caution contd… <ul><li>Pregnancy </li></ul><ul><li>CI with Halofantrine or within 2 months of mefloquine </li></ul><ul><li>Compromizes typhoid vaccine </li></ul><ul><li>Not with drugs which affect cardiac conduction </li></ul><ul><li>CI in jobs require motor coordination </li></ul>
    39. 40. Primaquine <ul><li>History : Lead to Identification of G6PD def. </li></ul><ul><li>Antimalarial action : </li></ul><ul><li>Effective against tissue forms[Bothe] and gametocytes. </li></ul><ul><li>Not against erythrocytic forms </li></ul><ul><li>Moa: Not known[Metabolites are toxic to parasites ?] </li></ul><ul><li>PK : only oral. Parenteral cause Hypotension </li></ul>
    40. 41. Primaquine contd… <ul><li>Radical cure of P.V. & P.O. </li></ul><ul><li>Terminal prophylaxis (just before or soon after leaves endemic area) </li></ul><ul><li>P.jiroveci with clindamycin </li></ul>
    41. 42. Primaquine contd… <ul><li>ADE : Hemolysis in G-6-PD def., anemia, methemoglobinemia </li></ul><ul><li>G-6-PD Def-200 million </li></ul><ul><li>India-Tirbals-Jharkhand, AP, MP, Assam </li></ul><ul><li>Spot tests available </li></ul><ul><li>Passage of dark urine-Stop </li></ul><ul><li>Pregnancy-Fetus deficient in G6PD </li></ul><ul><li>Risk is more with RA, SLE </li></ul><ul><li>Offers protection against severe malaria </li></ul><ul><li>More than 30mg/day repeated blood counts/urine for Hb. </li></ul>
    42. 43. G6PD Glucose Glucose-6-Phospate 6-Phoshogluconate Hexokinase NADP NADPH GSSG GSH Defeciency GSH DEF. Hemolysis No protection For RBC’s Against Oxidative substances Hemolysis
    43. 44. Proguanil(Chloroguanide) <ul><li>Proguanil Cycloguanil (Triazine) </li></ul><ul><li>Anti-malarial: </li></ul><ul><li>PF- Primary tissue stage & Erythrocytic forms </li></ul><ul><li>P.V.- Only erythrocytic stage </li></ul>
    44. 45. Proguanil(Chloroguanide) <ul><li>MOA: </li></ul><ul><li>Inhibits DHFR </li></ul><ul><li>Proguanil-intrinsic antimalarial activity </li></ul><ul><li>Accentuates action of Atovaquane </li></ul><ul><li>Therapeutic use : In combination with atovaquone-against resistant strains- prophylactic and curative (uncomplicated ) </li></ul><ul><li>Safe in pregnancy </li></ul>
    45. 46. Atovaquone <ul><li>Antiparasitic effect: </li></ul><ul><li>RBC forms of plasmodia, Early liver forms of FP, T.Gondii, P.Carinii, Babesia </li></ul><ul><li>MOA: Inhibits ATP and pyrimidine synthesis, collapse of mitochondrial membrane potential[Potentiated by Proguanil] </li></ul><ul><li>Resistance: Common when used alone </li></ul><ul><li>PK: Absorption increased by fatty food. 94% excreted unchanged in bile [E.H.circculation] </li></ul>
    46. 47. Atovaquone <ul><li>Uses: </li></ul><ul><li>Treatment and prophylaxis of resistant PF malaria, </li></ul><ul><li>T.gondii, </li></ul><ul><li>P.carinii </li></ul><ul><li>Babesia </li></ul><ul><li>Proguanil : Atovaquone – 100:250mg </li></ul>
    47. 48. Pyrimethamine <ul><li>Antiprotozoal action: </li></ul><ul><li>RBC forms –plasmodia, Pre-erythrocytic </li></ul><ul><li>T.Gondii [with S.D, high doses with Leucovorin] </li></ul><ul><li>MOA: DHFR inhibitor </li></ul><ul><li>Use: </li></ul><ul><li>Along with ( 25 : 500 ) sulfadoxine (folate synthetase inhibitor). Synergistic </li></ul><ul><li>Not for prophylaxis </li></ul><ul><li> Only tt of resistant strains of P.F. With sulfadiazine for T.Gondii. </li></ul><ul><li>Toxicity: due to Sulfa </li></ul>
    48. 49. Artemisinin Derivatives <ul><li>Sesquiterpine Lactone Endoperoxide derived from weed ARTIMISIA ANNUA (QING HAO) </li></ul><ul><li>Used by Chinese for 2000 yrs. </li></ul><ul><li>Derivatives: </li></ul><ul><li>1. Artesunate </li></ul><ul><li>2. Artemether </li></ul><ul><li>3. Arteether </li></ul><ul><li>4. Dihydroartimisinin </li></ul>
    49. 50. Artemisinin Derivatives….. <ul><li>Anti-malarial action : </li></ul><ul><li>1.Only against RBC forms and gametocytes </li></ul><ul><li>2.Not against tissue forms </li></ul><ul><li>3.Short acting, Recrudescence high, therapy prolonged even after disappearance of parasites from blood. </li></ul>
    50. 51. Artemisinin Derivatives….. <ul><li>MOA: </li></ul><ul><li>I Step </li></ul><ul><li>Heme iron in parasite </li></ul><ul><li>Cleaves endoperoxide bridge, </li></ul><ul><li>II Step </li></ul><ul><li>Carbon centerd radical is produced </li></ul><ul><li>Toxic to parasites </li></ul>
    51. 52. Artimisinin <ul><li>PK </li></ul><ul><li>Oral, i.v., Rectal-routes </li></ul><ul><li>Induce their own CYP450 </li></ul><ul><li>Resistance </li></ul><ul><li>No resistance </li></ul><ul><li>Resistance to Chlo. Paradoxically increases sensitivity to Artimisinin </li></ul><ul><li>ADE: </li></ul><ul><li>Allergic </li></ul><ul><li>Embryotoxic in animals, Cardiotoxic </li></ul>
    52. 53. Artemisinin Derivatives…. <ul><li>Therapeutic uses: </li></ul><ul><li>Oral: Uncomplicated Chloroquine/MDR malaria </li></ul><ul><li>Parenteral: Severe complicated F.P.Malaria </li></ul><ul><li>Not for prophylaxis, or P.V. or chloroquine sensitive F.P. </li></ul><ul><li>Only with combinations-longer acting drug. </li></ul>
    53. 54. Quinine Vs Artimisinin <ul><li>Quinine DOC in severe/complicated malaria </li></ul><ul><li>Artimisinin--- </li></ul><ul><li>Faster parasitic clearance </li></ul><ul><li>Safe, better tolerated </li></ul><ul><li>Simple dosing schedule </li></ul><ul><li>High efficacy, low mortality </li></ul>
    54. 55. ACT-Artemisinin based Combination Therapy <ul><li>To exhaust parasite burden </li></ul><ul><li>Short acting high efficacy drug to quickly kill 95% of parasites </li></ul><ul><li>Long acting drug for 7 days[Small parasite load, reduced chances of selecting mutants </li></ul><ul><li>ACT is the choice. Why? </li></ul><ul><li>Rapid clinical, parasitological cure </li></ul><ul><li>Low recrudescence </li></ul><ul><li>No resistance(Combination prevents) </li></ul><ul><li>Good tolerability </li></ul><ul><li>Combination regimens: Ref.KDT 6 th Ed. </li></ul>
    55. 56. Chemoprophylaxis Type Drug Before Entering After Leaving Chloroquine Sensitive Chloroquine po 4 500mg once a week 1-2weeks 4 weeks Resistant strains Pro+Ato(Malarone) 1tab/d 1-2 days 7 days Mefloquine 250mg/week 1-2 weeks 4 weeks Doxycycline 100mg 1Tab o.d. 1 day before 4 weeks
    56. 57. Chemoprophylaxis: Indications <ul><li>Special risk groups: </li></ul><ul><li>Non-immune travellers </li></ul><ul><li>Non-immune persons living in endemic areas </li></ul><ul><li>Pregnancy- After 1 trimester (Chloroquine, Proguanil, Quinine) </li></ul><ul><li>Terminal prophylaxis -Primaquine 30mg/day during last 14 days of chloroquine prophylaxis Or Chloro500+Prim45mg/week X 8 weeks </li></ul>
    57. 58. <ul><li>Standby Tt.[?Presumptive Tt.]: </li></ul><ul><li>Travellers within 24 h of symptoms[Presumed as malaria] </li></ul><ul><li>No chlo. prophylaxis ->Chlo or Meflo </li></ul><ul><li>Chlo ->Meflo or quinine </li></ul><ul><li>Meflo ->Quinine </li></ul><ul><li>Doxy ->Meflo </li></ul><ul><li>Malarone ->Doxy+Quinine </li></ul>
    58. 59. Prophylaxis in Pregnancy <ul><li>Travellers </li></ul><ul><li>Avoid travel[Pregnant or likely to become pregnant!!] </li></ul><ul><li>Chlo or Proguanil+F.A </li></ul><ul><li>Or Meflo in II, III trimester </li></ul><ul><li>Doxy, Ato, Prim. CI. </li></ul><ul><li>Mosquito net </li></ul><ul><li>Intermittent Preventive Treatment [IPT]: </li></ul><ul><li>Pregnant in endemic areas </li></ul><ul><li>Pyr+Sulfa </li></ul><ul><li>2-3 doses </li></ul><ul><li>I dose after quickening-II trimester </li></ul><ul><li>Further at 1 month intervals </li></ul>
    59. 60. Treatment Guidelines <ul><li>Malaria-Med.emergency </li></ul><ul><li>Clinical exp is the guide </li></ul><ul><li>Chloroquine d.o.c for sensitive strains </li></ul><ul><li>Oral route preferred, chlo.can be given iv with precautions </li></ul><ul><li>48-72 h-clinical improvement. </li></ul><ul><li>Parasites cleared within 7 days </li></ul><ul><li>If not-drug resistance </li></ul><ul><li>In Chlo. Resistance- d.o.c is quinine/Artimisinin </li></ul><ul><li>MDR-quinine & antifolates,T.c </li></ul><ul><li>Iv until tolerates oral route </li></ul>
    60. 61. Guidelines…. <ul><li>Children are small adults! Reduced dose, No TC </li></ul><ul><li>Ato-Pro. Only for more than 11 kg. </li></ul><ul><li>Pregnancy-Chlo, proguanil </li></ul><ul><li>Quinine with precautions for hpoglycemia </li></ul><ul><li>Antifolates, TC, artemisinin, atovaquone, primaquine avoided </li></ul><ul><li>Mefloquine if necessary </li></ul><ul><li>Lactating mother- all except ato-prog., tested for G6PD if primaquin to be used </li></ul>
    61. 62. Severe malaria Oral not possible Any species Non-Falciparum Falciparum P.Vivax Chlo Resistant F.P. Chlo Sensitive F.P. Chlo Resistant P.Vivax Chlo Sensitive Primaquine for Radical cure
    62. 63. Treatment-Chloroquine sensitive: P.V . <ul><li>Chloroquine po 4 1 Tab=250mg salt or 150mg base </li></ul><ul><li>Clinical cure- 0h - 4Tab stat </li></ul><ul><li>6h - 2 Tabs </li></ul><ul><li>24h - 2 Tabs </li></ul><ul><li>48h - 2 Tabs </li></ul><ul><li>Radical cure : Primaquine 15mg/d X 14 days. Primaquine C.I in G6PD def. </li></ul>
    63. 64. Treatment-Chloroquine Resistant: P.V .[Rare] <ul><li>Quinine 600mg 8 th hrly X 7 days </li></ul><ul><li>+ </li></ul><ul><li>Doxy 100mg daily X 7 days </li></ul><ul><li>+ </li></ul><ul><li>Primaquine </li></ul>
    64. 65. Treatment-Chloroquine Sensitive: FP .[Rare] <ul><li>Chloroquine:[250mg] </li></ul><ul><li>0h - 4Tab stat </li></ul><ul><li>8h - 2 Tabs </li></ul><ul><li>24h - 2 Tabs </li></ul><ul><li>48h - 2 Tabs </li></ul><ul><li>+ </li></ul><ul><li>Primaquine 45 mg single dose[gametocidal] </li></ul><ul><li>OR </li></ul><ul><li>Sulfadoxine/Pyrrimethamine 3 Tab + Primaquine[Chlo not tolerated] </li></ul>
    65. 66. Treatment-Chloroquine Resistant: FP <ul><li>Artesunate 100mg BDx3days </li></ul><ul><li>+ </li></ul><ul><li>Sulfadoxine/Pyrimethamine 3 tab single dose </li></ul><ul><li>OR </li></ul><ul><li>Mefloquine 750mg on ii day-500mg on iii day. </li></ul><ul><li>(Sulfadoxine500/Pyrimethamine25) </li></ul><ul><li>Artemether 80mg </li></ul><ul><li>+ Lumefantrine 480mg BD x 3 days </li></ul><ul><li>Quinine 600mg 8 th hrly x 7 days </li></ul><ul><li>+ Doxycycline 100mg daily x 7 days </li></ul>
    66. 67. Severe malaria <ul><li>Cerebral malaria : </li></ul><ul><li>Severe anemia </li></ul><ul><li>Renal failure </li></ul><ul><li>Pulmonary edema </li></ul><ul><li>Shock </li></ul><ul><li>Metabolic acidosis </li></ul><ul><li>Hemoglobinuria, jaundice </li></ul><ul><li>Hyperpyrexia </li></ul><ul><li>Hyperparasitemia </li></ul>
    67. 68. Severe <ul><li>The single most important step in the management of severe malaria is IMMEDIATE INITIATION OF APPROPRIATE PARENTERAL TREATMENT </li></ul>
    68. 69. Severe and complicated F.P.Malaria <ul><li>Artesunate 2.4mg/Kg i.v or i.m. » 12 hrs » 24 hrs » OD x 7days [Change to oral ACTx3days, if possible] </li></ul><ul><li>Or </li></ul><ul><li>Artemether: 3.2mg/Kgi.m » 1.6mg/Kg x 7days [change….] </li></ul><ul><li>Or </li></ul><ul><li>Arteether: Same as above. But 4 days </li></ul><ul><li>Or </li></ul><ul><li>Quinine diHCL:20mg/Kg in 10ml/Kg of dextrose infused 4hrs » 10mg/Kg for 4hrs every 8hrs » Oral quinine10mg/kgx 7days </li></ul><ul><li>+ doxy 100mg od oral or 3day oral ACT or pyrimethamine/Sulfadoxine </li></ul>
    69. 70. Treatment-Severe malaria <ul><li>Quinidine gluconate- </li></ul><ul><li>10mg/kg in 300ml of N.S over 2-3h (max600mg) </li></ul><ul><li>↓ </li></ul><ul><li>0.02mg/kg/.mt infusion for 24 h </li></ul><ul><li>↓ </li></ul><ul><li>Oral quinine sulfate 600mg tid X 7 days </li></ul><ul><li>AND Adjunctive therapy oral </li></ul><ul><li>Doxy 100mg bd </li></ul><ul><li>or </li></ul><ul><li>Clindamycin 20mg/kg/day X 7days </li></ul><ul><li>or </li></ul><ul><li>Pyr+Sulfa 3 tab on last day of quinine </li></ul>
    70. 71. Treatment-Chloroquine resistance <ul><li>Quinine 10mg/kg/day tid X 7 days </li></ul><ul><li>or </li></ul><ul><li>Mefloquine 750mg, repeat 500mg after 12 h. </li></ul><ul><li>or </li></ul><ul><li>Artesunate 100mg bid followed by 100mg od X 5 days [ACT?] </li></ul><ul><li>or </li></ul><ul><li>Pro + Ato 4 tab od X 3 days </li></ul>
    71. 72. Malaria Vaccine <ul><li>Reduce severity and complications of malaria </li></ul><ul><li>Tried in children less than 5yrs, in Africa </li></ul><ul><li>Reduces mortality and morbidity </li></ul>
    72. 73. Malaria Vaccine <ul><li>Sporozoite vaccine-Prevents infection-RTS,S/ASO2A </li></ul><ul><li>Asexual RBC form[Merozoite] Vaccine- Reduces severity-MSP-1 </li></ul><ul><li>Transmission blocking Vaccine-Against sexual forms in mosquito gut </li></ul><ul><li>Prevents development </li></ul><ul><li>Vaccines against toxins-Disease attenuation </li></ul><ul><li>Multiantigen, Multistage vaccine </li></ul>
    73. 74. Other drugs <ul><li>Halofentrene </li></ul><ul><li>} Drug resistant </li></ul><ul><li>Lumefentrene </li></ul><ul><li>Bulaquine……Primaquine </li></ul><ul><li>Amodiaquine…..Chloroquine </li></ul><ul><li>Dapsone….With pyremethamine </li></ul><ul><li>Fosmidomycin-apicoplast inhibitor </li></ul>
    74. 75. MDR Malaria <ul><li>“ Resistance to more than 3 or more anti-malarials of different chemical classes of which 2 are 4-aminoquinolines and diaminopyrimidine” </li></ul><ul><li>(Wernsdorfer et al, 1994). </li></ul><ul><li>Exposure of Plasmodium falciparum to sub-lethal doses of antimalarial drugs </li></ul>

    ×