1. AU, ASOHH, Dept OF INT. MEDICINE Yr-III ( C- I ) MEDICALSTUDENTS LECTURE ON MALARIA04 JUL 2011 GC , 8-9AM NUWAMA BIFA , MDTOPIC ---- MALARIAOBJECTIVE - at the end of this session students will be able to=Mention epidemiology of malaria = Describe the pathogenesis of malaria.= Identify the clinical scenarios of malaria.

2. CONTENT- introduction 1 Epidemiology 5 Etiology and pathogenesis 10 Clinical manifestation30 Diagnosis5 Treatment outline 3 Prevention 5 3. INTRODUCTION Malaria is a protozoal disease transmitted by the bite of infected Anophles mosquito and the most important parasitic diseases of humans, with transmission in >107 countries ( >3billion pop) and causing 1-3million deaths/yr , 150-300deaths/hr. 4. Introd .. Has now been eliminated from USA, Canada,Europe & Russia ,But remain heavy burden on tropical communities and danger to traveler. Critical approach to reduce malarial morbidity and mortality burden are : more sensitivediagnostic tools, prompt treatment ,and improvedpersonal protection and vector control . 5. EPIDEMIOLOGY Malaria occurs throughout tropical regions of the world , with p.falciparum causing largest burden, followed by p.vivax and p.malariae sub-sahara and p.ovale west Africa However, epidemiology of malaria is complex and vary considerably within small geographic areas. 6. Epidemio Endemicity : defined by parasitemia rates or palpablespleen rates in children of 2-9yrs Hypo endemic 75% 7. Epid . Both hyper- and holoendemic are X ed constant,frequant year round infection ,called stable transmission. People sustain >1 infectious mosquito bite/day and are infected repeatedly throughout theire lives. Adults are asymptomatic( immunity developed) ,morbidity and mortality thus considered in children and pregnants. 8. Entomologic inoculation rate( EIR) :number of infectious mosquito bite/person/yr.Has seasonal / geographic difference. EIR 50/yrhigh transmission area/stable transmission 9. Epid Principal determinants of malaria epidemiology: Vector density (No of vectors) X of Anophles Gambiae found in high density, readily breed. Human-biting-habit (in/outdoor) ---square of No humanbites/day/mosq. Logivity of vector (half life ) ----note; sporogony takes 8-30days. 10. ETIOLOGY Parasites ---Greece word, mean in close association with another organism of different species ,hostProtozoa : eukaryotic, unicellular(Plasmodium,leishmania ,toxoplasm,E.histolyt, Giardia,isospora,cryptosporidiu,T.vaginalis )Helminths ( helmins-worm ) : metazoa. Cestoda(tapeworm) e.g taenia sp. ,echinococcus Trematoda(flukes) e.g schistosoma (blood flukes) 11. Nematoda( roundworm ) ; intestinal and tissueArthropods : ectoparasite ; temporary/permanent Arachnida ; ticks and mite Insecta ; lice,bugs,fleas ,mosquito and flies Mosquito---Anophles,culex,Aedes,simulum,phlebotomy , Anophles >400 sp. Out of which A.gambiae plasmodium PLASMODIUM ; 4 SP. :P.falciparum ,p.vivax ,p.ovale ,p.malariae -all are humans infective,transmitted by infected anophles , Same pathogenesis. 12. MODE OF TRANSMISSION OF MALARIA 1,bite of plasmodium vector,Anophles gambiae (almostall case)Mosquito meal,ingest gametocyteszygote(in the midgut)ookinete penetrate gut wallhemolymphsalivary glandsporozoite(motile) through saliva inoculated into noninfectious indl uponnext bite.Takes 8-30days to complete the sexual stage in mosquito.Note; human stage is asexual. 13. Transm 2,blood transfusion ,by needle-stick injury(drug abusers),organ transplant_ ,congenital . Noincubation period in these modeof transmission and rare in occurance 14. PATHOGENESIS OF MALARIAInoculation of sporozoite(anophles bite)Liver (within 15-45)few sporozoite is infective,10p.f, hepatocytes invaded,asexual reproduction begin( tissue schizogony);single sporozoite gives 10000-30000merozoites tissue schizont ruptures(6-16days later) merozoites release into blood 15. Pathog RBCs invaded,merozoite attaches to receptor molecule on RBCs and species-specific (erythrocytic stage ; ring ,trophozoite ,mature trophoz(pigmented)schizont ,merozoite) , asexual multiplication(erythrocytic schizogony) rupture(q48-72hrs) merozoites released and re-invade another RBCs. 16. RBCs change : - intracellular protien(Hgb) degraded, Cell membrane altered ; transport property , Irregular shape , flexiblity lost,become antigenic Particularly, p. falciparum:form knobs =antigenic-variant ,whichHelps as adhensive. 17. Pathog +Cytoadherence----on venules and capillariesendothelium.+Rosetting------pf parasitized RBCS adherence on uninfected RBCs+Agglutination----on another parasitized RBCs 18. Pathog NOTE; cytoadherence,rosetting,and agglutination arehallmerk of falciparum malaria pathogenesis ,result insequestration parasitizedRBCs into microcirculation,vital organs particularly brain ,placeta and result insevere diseases. 19. HOST RESPONSE ; Nonspecific defense involved(Abs-tosporozoite, merozoite,malaria toxin,fertilization,Cell-mediated immunity to erytrocytic parasite )Splenic immunity -sequestration and clearance.Genetic protection-e.g Hgb and RBCs-Ag Hgb ; sickle cell (HgbS),HgbC,HgbF,B-thalassemia RBCs-Ag ; duffy chemokine receptor G6PD 20. CLINICAL MANIFESTATION OF MALARIA -begin at erythrocytic stage -vary with geography,epidemo ,immunity,age and p.species. -incubation period ( t inoculation clinical m.)-vary among p.spp.f =6-16days ,p.v and p.ov =10-21days ,p.m=21-42d months,even yrs 21. CM clinical form : *non-falciparum /benign malaria*uncomplicated falciparum malaria*severe complicated malaria*chronic complication of malaria 22. Clinical manifest. Cond presentation:non-falcip & uncomplicated falcip malaria-early symptoms ---nonspecific;headache,vomiting,abd pain,diarrh-classic --- paroxysms 0f fever spike,chills and rigors at regularp.v / p.ov --------- tertian fever(q48hrs)p.f ------------------malignant tertian feverp.m ---------------quartan fever(q72hrs) 23. CM :severe complicated falciparum malariaDef: acute life-threating malaria with hyperparasitemia >5-10%parasRBCs / _>100,000 parasites/ microlit and any SSx of organ dysfunction.-young children,elderly,non-immune travelers,pregnant,malnuri . ,RVI ,splenectomy are at high risk.-paras virulence,host immunity,and t b/n onset and Rxare important factors. 24. CM..condClinical criteria for severity cerebral malaria coma 30 without any other c hypoglycemia acidosisAcute renal failure 25. Criteria for severity Pulmonary edema/ARDS Severe anemia;NCNC ,thrombocytopenia,DIC ,(Thrombosis and bleeing) Liver injury Falciparum malaria in pregnancy 26. Chronic complication of malaria Hyperreactive malarial splenomegaly ; response to chronic/repeated infection Anemia , NCNCPresented with dragging LUQ abd pain& SSx of anemia 27. DIAGNOSIS OF MALARIA -clinical ,but no pathognomonic SSx of malaria -Light microscope : gold standard ,(Giemsa/Wrights stain) ;determine sp. ,parasitic density ,& helps to monitor therapy. -Rapid diagnostic test (RDT) : immunotochromatography containing Ab-specific to different epitopes & detect parasitic Ag proven by microscope. 28. Dx thin BF : thick BF : -other lab. Test : Hgb, periphmorphology,RBS,RFT,LFT,Serum e ,LP & CSF analysis(if indicated). 29. TREATMENT OUTLINE OF MALRIA :1, Non-falciparum malaria, A, chloroquine(10mg/kg po ,then 5mg/kg at 12,24,36,hrs) followed by primaquine(0.25mg/kg po/d/14d) in CQ sensitive regions. B, artemisinin-based combination therapy(ACT) ,in CQ resistant regions. 30. Rx-condUncomplicated falcip malaria, A, first line ,ACT for 3 days1, artemether-lumefantrine(coartem20/120)2, artesunate-amodiaquine(100/270)3, artesunate-mefloquine(50/250)4, atresunate-sufadoxina/pyrimethamine(50-500/25)5, dihydroartemisinin-piperaquine 31. Uncomp falc mal RxB, second line ,for 7days1, atresunate + TTC or Doxycy. Or Clindamy2, Quinine + TTC or Doxycy. Or Clindamy Pregnant- quinine + Clindamy/7d Lactating all except primaqu,TTC&Doxycy. 32. Rx-cond -severe complicated malaria :1,Quinine Iv ; loading 20mg/kg/4hrs in 5%DNS,then 12hrslater maintenance 10mg/kg/4hrs TID until pt can take orally full course of ACT .2,Artesunate Iv /IM ; 2.4mg/kg loading, 1.2mg/kg at 12,24hrsthen daily until pt take po. 33. Rx-cond3- if no option ,quininedihydrochloride IM or artemether IMcan be used.4-supportive treatment ; Rx hypoglycemia, anaemia, fever,coma care, Chronic malaria :Chloquine for long duration , 6mosSplenectomy 34. PERVENTION ;Def ; control , elimination ,eradication, CONTROL :reduction of disease incidence and prevalence tolevels that do not pose a threat to public , MDG 75% / 2015.Appropriate Rx, personal protection,vector control & vaccine ELIMINATION :reduction of incidence and transmission tozero in humans in a defined geographic area. ERADITION : global elimination of human disease . 35. PrevenCHALLENGES : -Increase resistance of malarial parasites to chemotherapy-Increasing resistance of the Anopheles to insecticides-Ecologic and climate changes-Increase in international travel to malaria-endemic areas bynon-immune travelers 36. THE END !THANK YOU ! 37. REFERENCES : Harrisons principles of internal medicine ,17th editon,2008 World health organization guidelines for the treatment of malaria,2nd edition ,2010 UpToDate17.3 Microbiology-ColouAtlas-2005.