1.Aduragbenro Adedapo

2. Malaria Globally 3.3 billion people are at risk of malaria 0.25 billion affected, 900 000 deaths annually (WHO,2009) 80-90% of the deaths occur in Africa (WHO, 2012) High Risk Groups Children under 5 years Pregnant women (Maternal anaemia, still birth, LBW) HIV/AIDs Non-immune travellers 3. Aetiological Agent of malaria in man Plasmodium falciparum, P. malariae, P. ovale and P.vivax cause malaria in humans. P. Knowlesi, monkey malaria parasite, have been reported to cause human malaria in parts of SouthEast Asia. Potential cause of malaria for travellers 4. Malaria Parasite Genome Complete genome sequence has been determined for: P.falciparum, P.vivax and P.knowlesi 5. Malaria mode of transmission Bite of female Anopheles mosquitoOthers: Congenital (mother to child) Blood transfusion Contaminated needle prick 6. Life cycle of malaria parasite In mosquitoes Sexual ------- sporozites In humans Liver stages (Primary, hypnozoites P.vivax & P.ovale) Red blood cells asexual and gametes 7. Life cycle of malaria parasite (wikiped) 8. Clinical Features of Malaria Fever Malaise Headache Myalgia Anorexia Vomiting Bitter taste in the mouthOther symptoms: vague abdominal pain, epigastric pain, pruritus, dry cough, lethargy 9. Malaria diagnosis Clinical: least expensive imprecise but the basis of treatment when laboratory support is out of reach 10. Parasite-based diagnostic methods Microscopy of Giemsa stained blood smears Alternatives: detection of malaria antibodies by indirect immunofluorescence assay (IFA); enzyme-linked immunosorbent assays (ELISA) Detection of malaria antigens Immunochromatographic assay: basis of rapid diagnostic tests (RDTs) Parasight-F test, OptiMAL IT Fluorescent stain Quantitative Buffy Coat (QBC) Molecular methods: DNA probes and polymerase chain reaction 11. Malaria diagnosis Microscopy is the gold standard: for promptparasitological confirmation alternatively by rapid diagnostic tests (RDTs) Treatment solely on the basis of clinical suspicion should only be considered when a parasitological diagnosis is not accessible. 12. Recommended Interventions Vector Control- Insecticide Treated Mosquito nets,Indoor Residual Spraying, +/- larval control Chemoprevention for vulnerable group viz pregnant women & infants (IPTp, IPTi) ; non-immune Confirmation of malaria diagnosis microscopy or rapid diagnostic tests Timely treatment use appropriate antimalarial drug 13. Management options Prevention Prophylaxis Therapy: Uncomplicated malaria, severe malaria,malaria in special conditions Orthodox medicine; traditional drugs (Neem or dongoyaro etc) Home management of malaria (HMM) Vaccines??? 14. Treatment of malaria Artemisinin based combination therapy (ACTs): first-line treatment for P. falciparum malaria. P. vivax malaria : chloroquine where it is effective, or an appropriate ACT in areas where P. vivax is resistant to chloroquine. Treatment of P. vivax should be combined with a 14day course of primaquine to prevent relapse. 15. 2006 Recommendations for uncomplicated P. falciparum malaria. Artemisinin-based combination therapies (ACTs) Examples are: artemether plus lumefantrine, artesunate plus amodiaquine, artesunate plus mefloquine, and artesunate plus sulfadoxine-pyrimethamine. Addition WHO 2010 guideline Dihydroartemisinin plus piperaquine (DHA+PPQ) 16. Second-line antimalarial treatment alternative ACT known to be effective in theregion; artesunate plus tetracycline or doxycycline or clindamycin; any of these combinations to be given for 7 days; quinine plus tetracycline or doxycycline or clindamycin; any of these combinations should be given for 7 days 17. Currently recommended ACTS for treatment of uncomplicated falciparum malaria in alphabetical order are: artemether plus lumefantrine, artesunate plus amodiaquine, artesunate plus mefloquine, artesunate plus sulfadoxine-pyrimethamine, dihydroartemisinin plus piperaquine. 18. artemether plus lumefantrine 6-dose regimen over a 3-day period. (514 kg: 1 tablet; 1524 kg: 2 tablets; 2534 kg: 3tablets; and > 34 kg: 4 tablets), given twice a day for 3 days. This extrapolates to 1.7/12 mg/kg body weight of artemether and lumefantrine, respectively, per dose, given twice a day for 3 days Available as a fixed-dose formulation tablets containing 20 mg of artemether and 120 mg of lumefantrine. 19. artesunate plus amodiaquine 4 mg/kg/day artesunate and 10 mg/kg/day amodiaquine once a day for 3 days Available as 50 mg of artesunate and 153 mg base ofamodiaquine separately & As fixed dose formulations containing 25/67.5 mg, 50/135 mg or 100/270 mg of artesunate and amodiaquine 20. artesunate plus mefloquine 4 mg/kg/day artesunate given once a day for 3 days and 25 mg/kg of mefloquine either split over 2 days as15mg/kg and 10mg/kg or over 3 days as 8.3 mg/kg/day once a day for 3 days Available as 50 mg of artesunate and 250 mg base ofmefloquine 21. artesunate plus sulfadoxinepyrimethamine 4 mg/kg/day artesunate given once a day for 3 days and a single administration of 25/1.25 mg/kgsulfadoxine-pyrimethamine on day 1 Available as 50 mg of artesunate tablet; and tabletscontaining 500 mg of sulfadoxine and 25 mg of pyrimethamine 22. dihydroartemisinin plus piperaquine 4 mg/kg/day dihydroartemisinin and 18 mg/kg/day piperaquine once a day for 3 days Available as 40 mg of dihydroartemisinin and 320 mgof piperaquine 23. Special conditions: Pregnancy First trimester: Quinine is safe in 1st trimester quinine plus clindamycin to be given for 7 days (artesunate plus clindamycin for 7 days is indicated if this treatment fails); an ACT is indicated only if this is the only treatment immediately available, or if treatment with 7-day quinine plus clindamycin fails or uncertainty of compliance with a 7-day treatment. Second and third trimesters: ACTs known to be effective in the country/region or artesunate plus clindamycin to be given for 7 days, or quinine plus clindamycin to be given for 7 days. 24. Pregnancy - first trimester Quinine plus clindamycin for 7 days (and quininemonotherapy if clindamycin is not available). Artesunate plus clindamycin for seven (7) days is indicated if this treatment fails 25. Caution in Pregnancy! Quinine is associated with an increased risk ofhypoglycaemia in late pregnancy, and it should be used only if effective alternatives are not available. Primaquine and tetracyclines should not be used in pregnancy 26. Lactating women & children Lactating women: Standard antimalarial treatment (including ACTs) except for dapsone, primaquine and tetracyclines. Infants and young children: ACTs for first-line treatment with attention to accurate dosing and ensuring the administered dose is retained. 27. Caution in lactation and children!! Tetracycline is contraindicated in breastfeedingmothers because of its potential effect on the infants bones and teeth. Primaquine should not be used in nursing women, unless the breastfed infant is not G6PD-deficient 28. Non-immune individuals Travellers returning to non-endemic countries: atovaquone-proguanil; artemether-lumefantrine; quinine plus doxycycline or clindamycin. 29. Non-immune individuals atovaquone plus proguanil (15/6 mg/kg [adult dose 4tablets] once a day for 3 days) Quinine, doxycycline (3.5 mg/kg once a day) or clindamycin (10 mg/kg twice a day) 30. Non-immune individuals Chemoprophylaxis already? The same medicine should not be used for treatment 31. Prevention of malaria in nonimmune Atovaquone/proguanil (Malarone) 250/100mg daily Chloroquine (if parasite sensitive) 300mg base weekly Doxycycline Hydroxychloroquine Mefloquine Primaquine100mg daily 310mg base weekly 228mg base weekly 30mg daily 32. Malaria and HIV Prompt treatment Treatment or intermittent preventive treatmentwith sulfadoxine-pyrimethamine should not be given to HIV-infected patients receiving cotrimoxazole (trimethoprim plus sulfamethoxazole) prophylaxis. Avoid amodiaquine-containing ACT regimens treatment in HIV-infected patients on zidovudine or efavirenz should, if possible, 33. Severe Malaria Demonstration of P. falciparum asexual parasitaemiain a patient + no other obvious cause of symptoms + the presence of one or more of the following clinical or laboratory features 34. Clinical Features of Severe Malaria impaired consciousness or unrousable coma prostration, i.e. generalized weakness so that the patient is unable walk or sit up without assistance failure to feed multiple convulsions more than two episodes in 24 h deep breathing, respiratory distress (acidotic breathing) circulatory collapse or shock, systolic blood pressure < 70 mm Hg in adults and < 50 mm Hg in children clinical jaundice plus evidence of other vital organ dysfunction Haemoglobinuria, abnormal spontaneous bleeding 35. Laboratory Parameters for Severe Malaria Hypoglycaemia (blood glucose < 2.2 mmol/l or < 40 mg/dl) Metabolic acidosis (plasma bicarbonate < 15 mmol/l) Severe normocytic anaemia (Hb < 5 g/dl, packed cellvolume < 15%) Haemoglobinuria Hyperparasitaemia (> 2%/100 000/l in low intensity transmission areas or > 5% or 250 000/l in areas of high stable malaria) Hyperlactataemia (lactate > 5 mmol/l) Renal impairment (serum creatinine > 265 mol/l) 36. Severe Malaria treatment options the cinchona alkaloids (quinine and quinidine) andthe artemisinin derivatives (artesunate, artemether and artemotil or beta arteether) 37. Severe Malaria For adults, artesunate IV or IM: quinine is an acceptable alternative if parenteral artesunate is not available. For children : artesunate IV or IM; quinine (IV infusion or divided IM injection); artemether IM (should only be used if none of the alternatives are available as its absorption may be erratic). 38. Non-immune/Travellers: severe malaria In the management of severe malaria outside endemicareas There may be unavailability or delay in obtaining artesunate, artemether or quinine parenteral quinidine if available should be given with careful clinical and electrocardiographic monitoring. 39. Severe Malaria - not recommended Parenteral chloroquine because of widespreadresistance & Intramuscular sulfadoxine-pyrimethamine 40. Quinine loading dose of quinine (i.e. 20 mg salt/kg body weight twice the maintenance dose) reduces the time needed to reach therapeutic plasma concentrations. The maintenance dose of quinine (10 mg salt/kg body weight) is administered at 8-h intervals, starting 8 h after the first dose administered as a slow, rate-controlled infusion (usually diluted in 5% dextrose and infused over 4 h 41. Quinidine Is more toxic than quinine, it causes hypotension andQT prolongation Only to be used if no other effective parenteral drugs are available. Its use requires electrocardiographic monitoring and frequent assessment of vital signs 42. Severe malaria (Rx - ctd) Give parenteral antimalarials in the treatment ofsevere malaria for a minimum of 24 h, once started (irrespective of the patients ability to tolerate oral medication earlier) and, thereafter, complete treatment by giving a complete course of ACTs 43. Severe malaria after parenteral drug(s) complete treatment by giving: artemether plus lumefantrine, artesunate plus amodiaquine, dihydroartemisinin plus piperaquine, artesunate plus sulfadoxine-pyrimethamine, artesunate plus clindamycin or doxycycline, quinine plus clindamycin or doxycycline. 44. Severe Malaria: pre-referral treatment options rectal artesunate, quinine IM, artesunate IM,artemether IM and promptly refer to an appropriate facility for further treatment. 45. Poser!!! Intravenous (IV) artesunate should be used inpreference to quinine for the treatment of severe P. falciparum malaria in adults. T3: Test. Treat. Track. initiative, urging endemiccountries and stakeholders to scale up diagnostic testing, treatment, and surveillance for malaria 46. Management of Antimalarial drug Resistance Therapeutic drug efficacy studies: to detect suspected artemisinin resistance artemisinin resistance: increase in parasite clearance time, as evidenced by 10% of cases with parasites detected on day 3 after treatment with an ACT Additional studies: (i) In vitro studies to measure the intrinsic sensitivity of parasites to antimalarial drugs (ii) Molecular marker studies to identify genetic mutations and subsequently confirm the presence of mutations in blood parasites (iii) pharmacokinetic studies to character drug absorption & drug action in the body 47. References Vinetz JM, Clain J, Bounkeua V, Eastman RT, Fidock D. Chemotherapy of malaria. In: Goodman and Gilmans Pharmacological Basis of Therapeutics, 12TH Edition, Laurence Brunton, Bruce Chabner and Bjorn Knollman (Editors). United States: McGraw-Hill, 2011 pp 13841418. World Health Organization. World Malaria Report, 2012. Available at: http://www.who.int/malaria/publications/world_malaria report_2012/wmr/2012_full_report.pdf WHO 2010 Guidelines for the treatment of malaria 2nd Edition National Guidelines for the diagnosis and treatment of malaria 2011 Wongrichanalai C, Barcus MJ, Muth S, Sutamihardja A, Wernsdorfer WH. A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT).. Am J Trop Med 2007; 77(6suppl) 119-27 48. THANK YOU Thank You For Your Attention All the best in all your endeavours practice andexaminations.