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Wacp int med revision course part 1 diagnosis and management of malaria
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Wacp int med revision course part 1 diagnosis and management of malaria

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  • 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 mosquito Others:  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 mouth Other 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 prompt parasitological 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 the region;  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.  (5–14 kg: 1 tablet; 15–24 kg: 2 tablets; 25–34 kg: 3 tablets; 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 of amodiaquine 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 as 15mg/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 of mefloquine
  • 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/kg sulfadoxine-pyrimethamine on day 1  Available as 50 mg of artesunate tablet; and tablets containing 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 mg of 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 quinine monotherapy 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 of hypoglycaemia 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 breastfeeding mothers because of its potential effect on the infant’s 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 – 4 tablets] 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  Primaquine 100mg daily 310mg base weekly 228mg base weekly 30mg daily
  • 32. Malaria and HIV  Prompt treatment  Treatment or intermittent preventive treatment with 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 parasitaemia in 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 cell volume < 15%)  Haemoglobinuria  Hyperparasitaemia (> 2%/100 000/μl in low intensity transmission areas or > 5% or 250 000/μl in areas of high stable malaria)  Hyperlactataemia (lactate > 5 mmol/l)  Renal impairment (serum creatinine > 265 μmol/l)
  • 36. Severe Malaria – treatment options  the cinchona alkaloids (quinine and quinidine) and the  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 endemic areas  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 widespread resistance &  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 and QT 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 of severe malaria for a minimum of 24 h, once started (irrespective of the patient’s 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 in preference to quinine for the treatment of severe P. falciparum malaria in adults.  “T3: Test. Treat. Track.” initiative, urging endemic countries 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 Gilman’s 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 and examinations.

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