history

• 1 ½ y boy

• Fever – 2 weeks– Intermittent– 39.5– Chills and rigor – sweating

history

• ? URTI

• Oral antibiotic( amoxicillin ), ( cefixime)

•

history

• Pallor , family history of G6PD• Normal urine • No cough ,SOB• No vomiting , diarrhea ,• Normal appetite • No jaundice • No skin rash• No abnormal movement

Examination

• Pale • Febrile• No LAP• ENT : N• RS: N• CVS: N• ABD: N• CNS: N

investigation

• CBC – WBC: 8.2

– NEUT: 36– LYMPH: 45

– HB : 7.2– PLAT: 70

• Retic: high

• G6PD: 6 ( 6-10) ??

investigation

• Malaria smear : +ve ( 1% parasitemia)

Hospital course

• Mefloquine ( 15 mg/kg then 10 mg /kg 12 later)

Hospital course

• Repeated malaria smear x3 : +ve

Hospital course

?!!

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

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

antimalarial drugs

• the quinolines and arylaminoalcohols

• the antifols

• the artemisinin derivatives

• the hydroxynaphthaquinones

• Antibacterial agents

• Quinolines and arylaminoalcohols• chloroquine,• amodiaquine,• quinine,• quinidine, • mefloquine,• halofantrine,• primaquine,• tafenoquine,• lumefantrine,• piperaquine, • pyronaridine

• Antifols• pyrimethamine, • proguanil, • chlorproguanil, • trimethoprim

• Artemisinin derivatives• artemisinin, • dihydroartemisinin,• artemether, • artesunate

• Hydroxynaphthaquinones• atovaquone

Artemisinins

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

Artemisinins

• sweet wormwood

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

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

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

ANTIMALARIAL PROPERTIES

• kill early gametocyte stages of development

• potential to interfere with mosquito transmission

Lancet 2000;355:352–7

MECHANISM OF ACTION

• free radicals

• inhibition of the malarial parasite’s calcium ATPase

J Med Chem 2004;47:2945–64

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

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

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

Rectal administration

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

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.

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

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.

Reversed chloroquines

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.

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

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

• Is it the time to recommend CQ-CP combination in KSA??!!

KSA and malaria

KSA

• 1st report of CQ resistant was in 1991 J Egypt Soc Parasitol. 1991 Aug;21(2):591-2

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.

• 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

Malaria treatment guideline in Saudi Arabia

!!!??????!!!

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