MALARIA

Over view  Basic understanding of malaria  Epidemiology  Symptoms  Diagnosis  Treatment  Prevention

 Malaria is a protozoan disease transmitted by the bite of infected female Anopheles mosquitoes.  Protozoan parasites of the genus Plasmodium  Four species:  P falciparum  P vivax  P ovale  P malariae

characteristicp.falciparump.vivaxp.ovulaep.malariae Severity of malaria Severe may be fatal Benign, rarely same Uncommon, benign Mild,occasional Duration of intra hepatic phase Average incubation period 7-14 days12-17 days15-18 days18-40days Duration of erythrocytic cycle Red cell preference Younger cellsRbc up to 14 days recticuocytesOlder cells

Transmission  Man is the only important reservoir  Vector is female Anopheles mosquito  Temperature: below 86º F, above 68º F  Rainfall: thrive in tropical areas  Altitude: rarely exist above 2000 meters  Terrain: coastal areas and lowlands with lots of freshwater breeding sites

Transmission  Mosquito vector: ANOPHELES  Transmission also possible through: 1.Blood transfusion 2.Contaminated needle 3.Organ transplant 4.Congenital

Susceptibility  Universal susceptibility  No absolute immunity  Partial immunity in areas of high endemicity

Pathogenesis  RBC destruction  Immune complexes and mediators  Capillary permeability  Tissue hypoxia

RBC Distruction  After invading an erythrocyte, the growing malarial parasite progressively consumes and degrades intracellular proteins, principally hemoglobin.  The potentially toxic heme is polymerized to biologically inert hemozoin, or malaria pigment.  The parasite also alters the RBC membrane by changing its transport properties, exposing cryptic surface antigens, and inserting new parasite-derived proteins.  The RBC becomes more irregular in shape, more antigenic, and less deformable.

 In P. falciparum infections, membrane protuberances appear on the erythrocyte's surface toward the end of the first 24 h of the asexual cycle. These “knobs” extrude a high-molecular-weight, antigenically variant, strain-specific, adhesive protein (PfEMP1) that mediates attachment to receptors on venular and capillary endothelium—an event termed cytoadherence.

 P. falciparum–infected RBCs may also adhere to uninfected RBCs to form rosettes and to other parasitized erythrocytes (agglutination). The processes of cytoadherence, rosetting, and agglutination are central to the pathogenesis of falciparum malaria. They result in the sequestration of RBCs containing mature forms of the parasite in vital organs (particularly the brain), where they interfere with microcirculatory flow and metabolism.

 P. vivax, P. ovale, and P. malariae show a marked predilection for either young RBCs (P. vivax, P. ovale) or old cells (P. malariae) and produce a level of parasitemia seldom >2%, P. falciparum can invade erythrocytes of all ages and may be associated with very high levels of parasitemia.

IMMUNE RESPONE  The specific immune response to malaria eventually controls the infection and, with exposure to sufficient strains, confers protection from high-level parasitemia and disease but not from infection.  As a result of this state of infection without illness (premunition), asymptomatic parasitemia is common among adults and older children living in regions with stable and intense transmission (i.e., holo- or hyperendemic areas).  Immunity is mainly specific for both the species and the strain of infecting malarial parasite. Both humoral immunity and cellular immunity are necessary for protection, but the mechanisms of each are incompletely understood

Plasmodium Species  P. falciparum  Most severe and prevalent  40-60% of cases  Widespread CHLOROQUINE resistance  Infects RBCs of all ages—Heavy parasitemia

 P. vivax  30-40% of cases  Liver phase  INFECTS YOUNG RBCs: LESS SEVERE THAN FALCIPARUM  P. ovale  Liver phase  INFECTS YOUNG RBCs  P. malariae  Can persist SUBCLINICALLY for extended periods of time  INFECTS OLD RBCs

Presentation  Fever96%  Chills96%  Headache 79%  Muscle Pain60%  Palpable liver33%  Palpable Spleen 28%  Nausea or vomiting23%  Abdominal pain/diarrhea 06%

Complicated Malaria  Hyperparisitemia: (>3%)  Hypoglycemia: (<60 mg/dl)  Severe anemia (hct < 21% or rapidly falling hct)  Renal failure  Hyponatremia  Cerebral malaria  Prolonged hypothermia  High output vomiting or diarrhea  Pregnancy

DIAGNOSIS u Gold standard: Multiple thick and thin smears u Dip stick tests u CBC –Anemia –Leukopenia, or leukocytosis –No eosinophilia

Treatment  CHLOROQUINE sensitive infections:  CHLOROQUINE 600 mg (2 tabs) P.O. initially  300 mg (1 tab) in 6 hrs  300 mg (1 tab) QD for 2 days

 Uncomplicated CHLOROQUINE-resistant infections: Quinine 650 mg PO TID x 3 days and DOXYCYCLINE 100 mg PO bid x 7 days, OR MEFLOQUINE mg PO once  Complicated or severe infections I.V. QUINIDINE or quinine

 VIVAX and OVALE therapy should include PRIMAQUINE 15mg PO QD x 14 days  CDC now recommends: PRIMAQUINE 30mg PO QD x 14 days

Treatment Options For chloroquine sensitive Chloroquuine Primaquine For chloroquine resistance Sulfadoxine Quinine pyrimethamine Doxycycline Mefloquine Artesunate Artemether

WHO Guidelines For Malaria 2006 Treatment of uncomplicated malaria: Vivax malaria: (1) chloroquine 600mg ( 10mg/kg) followed by 300mg ( 5mg/kg) after 8 hours and then for next 2 days.( total dose 25mg/kg over 3 days)+primaquine 15mg (0.25mg/kg) daily for 14 days. (2)Quinine 600mg (10mg/kg) 8 hourly for 7 days+doxycycline 100mg daily for 7 days+primaquine (as above)

Chloroquine sensitive falciparum malaria: (1)Chloroquine (as above)+primaquine 45mg(0.75mg/kg) single dose (2) Sulfadoxine 1500mg(25mg/kg)+pyrimethamine 75mg(1.25mg/kg) single dose+primaquine 0.75mg/kg single dose

Chloroquine resistant falciparum malaria (1)A75mg single dose Or artesunate 100mg BD for 3 days+mefloquine 750mg (15mg/kg) on 2 nd day and 500mg (10mg/kg) on 3 rd day Or artemether 80mg +lumefantrine 480mg twice daily for 3 days. or Quinine 600mg (10mg/kg) 8 hourly for 7 days +doxycycline 100mg daily for 7 days rtesunate 100mg BD for 3 days+sulfadoxine 1500mg +pyrimethamine

Treatment of severe and complicated falciparum malaria: (1)Artemether 2.4mg/kg iv or iM followed by 2.4mg/kg after 12 and 24 hours and then once daily for 7 days Or artemether 3.2mg/kg iM on 1 st day followed by 1.6mg/kg daily for 7 days Or quinine loading dose: 20mg/kg and maintain 10mg/kg

ATC COMBINATIONS 1)Artesunate-mefloquine: Artesunate 100mg BD (4mg/kg/day)for 3 days+Mefloquine 750mg(15mg/kg) on 2 nd day and 500mg (10mg/kg)on 3 rd day.(total dose 25mg/kg) (2)artemether-lumefantrine(1:6) Artemether 80mg BD+lumefantrine 480mg BD for 3 days. (3)Artesunate-sulfadoxine+pyrimethamine Artesunate 100mg BD for 3 days+sulfadoxine 1500mg &pyrimethamine 75mg single dose