history 1 ½ y boy fever –2 weeks –intermittent –39.5 –chills and rigor –sweating
TRANSCRIPT
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history
• 1 ½ y boy
• Fever – 2 weeks– Intermittent– 39.5– Chills and rigor – sweating
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history
• ? URTI
• Oral antibiotic( amoxicillin ), ( cefixime)
•
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history
• Pallor , family history of G6PD• Normal urine • No cough ,SOB• No vomiting , diarrhea ,• Normal appetite • No jaundice • No skin rash• No abnormal movement
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Examination
• Pale • Febrile• No LAP• ENT : N• RS: N• CVS: N• ABD: N• CNS: N
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investigation
• CBC – WBC: 8.2
– NEUT: 36– LYMPH: 45
– HB : 7.2– PLAT: 70
• Retic: high
• G6PD: 6 ( 6-10) ??
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investigation
• Malaria smear : +ve ( 1% parasitemia)
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Hospital course
• Mefloquine ( 15 mg/kg then 10 mg /kg 12 later)
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Hospital course
• Repeated malaria smear x3 : +ve
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Hospital course
?!!
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WHO
• Malaria is the most significant parasitic infection in the world
• Approximately 2 billion people live in malaria-endemic areas
• malaria causes an estimated 300 to 500 million cases of acute illness each year
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WHO
• responsible for at least 20 percent of the mortality in young children
• approximately 3000 deaths per day
• Malaria has been estimated to cost Africa more than $12 billion US yearly
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antimalarial drugs
• the quinolines and arylaminoalcohols
• the antifols
• the artemisinin derivatives
• the hydroxynaphthaquinones
• Antibacterial agents
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• Quinolines and arylaminoalcohols• chloroquine,• amodiaquine,• quinine,• quinidine, • mefloquine,• halofantrine,• primaquine,• tafenoquine,• lumefantrine,• piperaquine, • pyronaridine
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• Antifols• pyrimethamine, • proguanil, • chlorproguanil, • trimethoprim
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• Artemisinin derivatives• artemisinin, • dihydroartemisinin,• artemether, • artesunate
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• Hydroxynaphthaquinones• atovaquone
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Artemisinins
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Artemisinins
• derived from a plant called sweet wormwood
• reported to have antipyretic properties more than 1500 years ago
• In 1971, a highly active chemical was obtained and is now called artemisinin
Chin Med J (Engl) 1979;92:811–16
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Artemisinins
• sweet wormwood
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Artemisinins
• Artemisinin is a highly crystalline compound that does not dissolve in oil or water
• Semisynthetic derivatives that have been chemically modified at the C10 position to produce artesunate, artemether, arteether, dihydroartemisinin, and artelinic acid
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ANTIMALARIAL PROPERTIES
• Artemisinins kill all species of plasmodium that infect humans
• The asexual stages of infection are the most susceptible
• artemisinins are active against the large ring stage of infection
• artemisinins also target tiny ring stages of infection
J Antimicrob Chemother 2002;50:751–4
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ANTIMALARIAL PROPERTIES
• Artemisinins inhibit metabolism of parasites more quickly than other antimalarials
• Potential benefit
• Artemisinins do not interfere with hepatic stages of parasite development
• no causal prophylactic value J Infect Dis 1996;173:691–8
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ANTIMALARIAL PROPERTIES
• kill early gametocyte stages of development
• potential to interfere with mosquito transmission
Lancet 2000;355:352–7
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MECHANISM OF ACTION
• free radicals
• inhibition of the malarial parasite’s calcium ATPase
J Med Chem 2004;47:2945–64
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CLINICAL APPLICATIONS
• treatment of uncomplicated and severe malaria• pregnant women
• study of over 500 women treated with artemisinins in Thailand no increase in rate of abortion, congenital abnormality, or stillbirth
Clin Infect Dis 2001;33:2009–16
• no evidence of significant resistance in clinical isolates
Postgrad Med J 2005;81:71–78
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Severe malaria
• Quinine vs Artemisinins• narrow therapeutic ratio• hyperinsulinaemic hypoglycaemia (more frequent
and severe in pregnancy) • prolongs the QTc interval• evidence of resistance in south east Asia • Rapid parasitic clearance
Trans R Soc Trop Med Hyg 2001;95:637–50
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Severe malaria
• Intravenous artesunate is the drug of choice for severe malaria, particularly if acquired in Asia
Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005967
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Rectal administration
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Rectal administration
• A study of 898 children with severe P falciparum malaria– Rectal quinine (20 mg/kg diluted to 30 mg/ml
in water solution) VS intramuscular quinine (12.5 mg/kg)
• efficacy outcomes did not differ BMJ. 2006 May 6;332(7549):1055-9
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Rectal administration
• A study of 110 children aged 6 months to 5 years who had cerebral malaria. – Patients were randomized to receive either intrarectal
or intravenous quinine • there was no difference in
– the clinical and parasitological outcomes
– coma recovery time,
– fever clearance time
– parasite clearance time.
– Mortality was similar in both groups
Clin Infect Dis. 2007 Dec 1;45(11):1446-52.
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Rectal administration
• a comparative study with parenteral quinine, rectal artesunate was efficacious in African children with moderate-severe malaria
Lancet 2004;363:1598–605
• rectal formulation of artesunate lead to rapid falls in parasitaemia that were indistinguishable from those seen after intravenous artesunate
Antimicrob Agents Chemother 2001;45:509–16
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Rectal administration
• Intrarectal quinine or artesunate are efficacious and could be used as an alternative in the treatment of childhood cerebral malaria, especially in situations in which intravenous therapy is not feasible.
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Reversed chloroquines
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Reversed chloroquines
• Chlorpheniramine was assayed for in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum
• chlorpheniramine exerts marked synergistic action on chloroquine against P. falciparum
• Chlorpheniramine also potentiated antimalarial action of mefloquine, quinine
• chlorpheniramine antagonism with artesunate was obtained
Parasitol Int. 2006 Sep;55(3):195-9.
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Reversed chloroquines
• A standard treatment CQ, alone or in combination with CP, to 117 semi-immune Nigerian children with P. falciparum observed for 28 days
• Treatment with CQ-CP combination resulted in a shorter parasite clearance time (2.0 +/- 0.5 days) and a higher cure rate (87.5%) compared to treatment with CQ alone (3.5 +/- 0.5 days; 66.7%)
Afr J Med Med Sci. 2004 Mar;33(1):77-81
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Reversed chloroquines
• five children who failed CQ and/or AQ treatment, were subsequently retreated and cured with a combination of AQ plus CP
» Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 102(3), June 2007
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• Is it the time to recommend CQ-CP combination in KSA??!!
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KSA and malaria
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KSA
• 1st report of CQ resistant was in 1991 J Egypt Soc Parasitol. 1991 Aug;21(2):591-2
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KSA
• P. falciparum isolates from malaria-endemic area of Jazan showed CQ resistance rate (89.5%)
• the highest percentage of chloroquine resistance ever recorded in Saudi Arabia
• 10.5% of isolates showed a PYR-SDX resistant
J Egypt Soc Parasitol. 2007 Apr;37(1):17-30.
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• In Yemen :– Chloroquine resistance was found in 47% of
isolated P. falciparum– Mefloquine resistance was found in 5.2%
Ann Saudi Med. 2007 Nov-Dec;27(6):432-6
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Malaria treatment guideline in Saudi Arabia
!!!??????!!!
THANK YOUTHANK YOU