FALCIPARUM MALARIA AN OVER VIEW D R .C.K.TALUKDAR MD.,DRM,FICP,FICN,FICC PRAGATI NURSING HOME NALBARI
MALARIA Basic considerations and clinicalfeaturesMalaria in man is caused by four distinctspeciesofmalaria parasite:* P.vivax,P.falciparum,P.malariae,P.ovale* P.Vivax & P.falciparum are resposible for most of theinfections found throughout the malarial belt.*P.malariae is widely distributed but is less common.*P.ovale is rare but in West Africa it seems to havereplaced P.vivax.*Malaria is estimated to kill between 1.5 and 2.7 millionpeople each year.*In an average one person, often a child below 5yrs. Ofage die in every 12 seconds.*Additional 300-500 million people contact the diseaseeach year(Butlon,1997)
MALARIAMILESTONES1600 B.C. References can be found in the writings400 Hippocrates’ description of malaria.Charaka and Sushrutha gave vivid descriptions of malaria & even associated it with the bites of the mosquitoes.1640 A.D. Huan del Vego – Cinchona bark for malaria treatment1696 Morton first detailed picture of Malaria.1717 Lanicsi Links malaria to bad air in swamps and thus originates the name malaria.1816 Gize-Extraction of quinine from cinchona bark1820 Pelletier and Caventou – extraction of pure quinine alkaloids 1880 Laveran identifies malarial parasite under microscope.1895 Golgi-Identification of P.vivax & P.malariae1889-90 Sakharov,Marchiafava,Celli-identification of P.falciparum
1897 Ronald Ross–Demonstration on malarial oocysts in gut of female anopheles mosquito 1934 Chloroquine synthesized by Germans. 1939 Paul Miller – Insecticidal properties of DDT 1944 Curd, Davey, Rose – Synthesis of Proguanil for treatment. 1950 Elderfield– Synthesis of primaquine. 1967 WHO- emphasis on control of malaria rather than global eradication of the disease. 1990’s Synthesis of quinine analogue mefloquine. Artemesinins obtained from Quinghaosu introduced for resistant malaria. 1994 Sequencing of P.Falciparum Genome begun 1999 WHO Recommends – Combined therapy to delay resistance development to anti-malarials
PLASMODIUM VIVAX1. Red cells containing parasites are usuallyenlarged.2. Schuffner”s dots are frequently present in the redcells as shown.3. The mature ring forms tend to be large andcoarse.4. Developing forms are frequently present.PLASMODIUM FALCIPARUM1. Red cells are not enlarged.2. Rings appear fine and delicate & there maybe several in one cell.3. It is unusual to see developing forms in peripheral blood films.4. Gametocytes have a characteristic crescent
PLASMODIUM MALARIAE 1.Ring forms may have a squarish appearance. 2.Band forms are a characteristic of this species.3.Mature schizonts may have a typical daisy head appearance with up to ten merozoites.PLASMODIUM OVALE 1. Only found in Africa. 2. Red cells enlarged. 3. Comet forms common. 4. Rings large and coarser.
MALARIA PATHOLOGY* * Pigmentation of various organs with haemozoin giving acharacteristic “SLATE GREY” Or “BLACK COLOUR”.* * Hyperplasia of the Reticulo-Endothelial system resultingfrom increased activity in order to deal with parasite andtheir product. * * Parasitized erythrocytes filling the Lumina of thecapillaries of the internal organs. This is particularly seen inP.falciparum infection. * * Vascular changes-dilatation of sinusoidal vessels,perivascular haemorrhages are seen in falciparum malaria. * * Degenerative changes of parenchyma cells due tohypoxia [ seen in falciparum malaria]. * * Effects of anaemia. * * Immunosupression has been observed in malarialinfection and this may lead to secondary bacterial infection.
THE SPLEENSpleen is enlarged,colour varies from slate gray to black,capsule is thin & stretched, consistency soft in acute caseswhile firm in chronic cases. “AGUE CAKE SPLEEN ”THE LIVERThe Liver is uniformly enlarged due to vascularcongestion and proliferation of reticuloendothelial cells.The colour varies from chocolate red to slate gray oreven black depending upon the stage of congestion anddeposition of the haemozoin pigment.BONE MARROWKIDNEYS
Does the Patient NeedHospitalization ?Seriously ill patients needing Hospitalization- Include:- Continuous vomiting andinability to retain oval drugs. Increasing Headache. Severe Dehydration. Poor general condition. Alteration of sensorium. Suspected cerebral malaria with unarousable Coma. Hyper pyrexia, convulsion. Pregnancy Oedema. Bleeding disorders.
COMPLICATIONS :Cerebral malaria and coma.Hyperpyrexia.Haemolytic Anaemia.Non cardiogenic pulmonary oedema(ARDS ) ;Acute tubular necrosis and renalfailure ;Acute Hepatomegaly and centrilobularnecrosis ;Hypoglycaemia ;An adrenal insufficiency like syndrome;Cardiac dysrhythmias ;Lactic acidosis .
Pathophysiology :of complicated malariaPathology associated with all malarial species is related to therupture of the infected RBC and release of haemozoin(Malarial pigment). An increased in reticulo-endothelial system is fond causinghepato-splenomegaly.Cytoadhence of infected red cells to the vascular endothelium &RBC’s causing rossetting-compromises microcirculatory flow.In cerebral malaria-due to sequestration of the infectederythrocyles in the cerebral microcirculation.Sequestration in cytiadherence of trophozoite and schizont infectederythrocytes to the endothelial cells of the deeper vascular beds ofthe vital organs-specially the brain,liver,gut,heart & placenta,
Table 1= Anti-malarial DrugDRUG Indications Dosage Side effects/ PrecautionsChloroquine Treatment Adults: Hepatic and/orTabs: 150/300mg Oral : renalSyp:50mg/ml Day 1=600mg stat dysfunction, 300mg after 6 hrsInj.:50mg/ml Vision Day 2 = 300mg OD Day 3 = 300mg OD problems, Injectable Psoriasis, IM = 10ml stat, Epilepsy, 5ml after 6 hrs., 5ml daily for 2 days Porphyria. Children: Oral : 10mg/kg stat, 5mg/kg after 6 hrs. Then 5mg/kg/day for 2 days Prophylaxis 300 mg OD weekly,2 wks Before entering endemic Area continue for 4 wks after leaving
Contd…. Table 1:- Anti-malarial DrugsDrug Indications Dosage Side effects/ precautionsSulphadoxine Treatment Adults :<50 kg 2 tabs. Unusual bleeding,Pyrimethamine Bruising rash, >50 kg 2 tabs.Tablets Fever, sore throat500mg Children 0.5-0.75 mg/kgsulphadoxine+25mg pyrimethamine per dose.Liquid: Prophylaxis Adults : 1 tab. Once wkly.250mgsulphadoxine+12.5mgpyrimethamine/5ml.Quinine Adults : Disturbed vision, tinnitus,nausea,300mg,600mg 300-600mg TID 5-7 days headache,tabs, Children : rash,300mg/ml inj. 25mg/kg/day div. Every 8 hrs for Special Precaution 7 days, Renal dysfunction, optic neuritis, myasthenia gravis, cardiac dysfunction
Contd.Drug Indications Dosage Side effects/ precautionsPrimaquine Radical cure Adults : Nausea,vomiting,weakness of vivax abd.pain,2.5,7.5,15mg 15mg/day x 14 days malaria Methhaemoglobinaemia,tabs. Along with standard Anemia, Chloroquine treatment Leucopaemia, Children : 25mg/kg/day div. G6PD test Every 8 hrs for 7 daysMefloquine Resistant Adults : Nausea,vomiting,diarrhoe a,dizziness,rash,250 mg tabs. malaria 15mg/kg single dose Somnolescence, Max.1259-1500mg or 750mg stat followed by another 250mg 6-8 hrs. Neuro-psychiatric Later symdrome, Children : neuropathy, vestibulopathy, 15-25mg/kg, single oral dose Prophylaxis circulatory disease 5mg/kg/wk
Contd….Artemether Resistant IM 3.2mg/kg initially then Cardio toxicity, 1.6mg/kg 12-24 hrs. for 3-7 days Blood changes, falciparum Adults : Oral tab.Day 1=80mg BD Raised liver40mg tabs. malaria, Then, 80mg OD for 2-5 days. Enzymes,80mg/ml inj. Severe Children : Day 1=1.6mg/kg BD Neurotoxicity. falciparum 1.6 mg/kg OD for 2-5 days malariaArtesunate Resistant Oral:Day 1 : 100mg BD Drug fever,rash Falciparum Day2-5 : 50mg BD Cardio toxicity,50mg tab. Malaria, Parenteral : 2mg/kg stat , Raised liver60mg inj. Severe 1mg/kg 12 hrly. Till oral enzymes, malaria. treatment possibleArteether Resistant Adult : Neurotoxicity Falciparum 150mg inj. IM once daily for 3 Nausea,150mg in 2ml malaria days. Dizziness,amp. Children : Depressed GIT activity 3mg/kg/day IM x 3 days.
Treatment of Resistant Malaria (Uncomplicated Resistant)1.Sulphadoxine-Pyrimethamine :- patients weighing >50kg. 3 tablets stat, patients weighing <50kg. 2 tablets stat, (provided patient has no sulpha allergy) + quinine 600mg TDS for 2 days.2.Quinine 600mg TDS or Quinine sulphate 10mg/kg/8 hrly for 7 days + Doxycycline 100mg BD or Tetracycline 500 mg BD for 7 days.3.Mefloquine 750 mg stat, followed by 750 mg after 6 hrs. (Pts. Weighing > 50 kg) or 500mg stat followed by 500mg after 6hrs. (Pts. Weighing < 50 kg.)
Treatment of ResistantMalaria (Complicated Resistant) Ideally all patients with complicated should be hospitalized. Inj. Quinine IV slowly in Dextrose. Higher loading dose is preferred relative to maintenance dose. In patients requiring more than 48 hours parenteral therapy, reduce the maintenance dose by ½ rd. In presence of renal failure; quinine dose should be halved after 48 hours. Inj. Artemether 160mg IM, then 80mg daily for 4 days
Artemether Dosage regimenRezart Route Adults Pediatric Day 1 Days 2-5 Day 1 Days 2-580 mg/ IM 1.6mg/kg 1.6 mg/kg 1.6 1.6Ampoule twice once mg/kg mg/kg twice Once60mg cap Oral 1.6mg/kg 1.6 1.6mg/kg twice 1.6mg/kg mg/kg once once twice
Comparative Efficacy : In Cerebral Malaria Parameter Arteether QuinineComa recovery time 24.33 38.87(hrs.) 6.67 27.27Mortality (%)
Arteether Dosage RegimenRezart-E Route Adults Pediatric Day 1 Days Day 1 Days 2 –3 2-3150 mg/ IM 150 mg 150mg/ 3mg/kg 3mg/kg/ ampoule day day
Bulaquine : A New generation Anti-malarial drug Bulaquine a derivative of primaquine developed by the Central Drug research Institute in collaboration with W.H.O., Advantage :- Bulaquine has a biological activity against the tissue schizont forms of Plasmodium Vivax having :- a. A better therapeutic window. b. Lesser side effects, c. A better therapeutic index as compared t current treatment available.
Mechanism of action of :Bulaquine In contrast to current Drugs, 8-Aminoquinolones are the only drug which act on the liver stage and prevent infection by killing liver stages of the parasite before merozoites reach blood Stream. Thus prevents emergence of either primary or secondary attacks. Bulaquine Inhibits protein synthesis in protozoa and indirectly inhibits Polymerisation of Amino acids by the Plasmodia. It has also high gametocidal action.
Dosage of Bulaquine :- ** 25 mg once daily for 5 days. ** Should be given with chloroquine for complete cure of Vivax malaria .INDICATION : For the treatment of Vivax malariaContra-indications: 1. Rheumatoid Arthritis. 2. Systematic Lupus erythematosus.Concurrent use of Drugs known to cause Haemolysis
Future of MalarialTreatment I. Gene Therapy. II. Malarial Vaccine. III. Genetic Mapping Plasmodium falciparum. IV. Low Interleukin-12 Activity in severe Plasmodium falciparum