AU, ASOHH, Dep’t OF INT. MEDICINE Yr-III ( C- I ) MEDICAL STUDENTS ‘ LECTURE ON MALARIA 04 JUL 2011 GC , 8-9AM NUWAMA BIFA , MD TOPIC ---- MALARIA OBJECTIVE - 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.
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.
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 sensitive diagnostic tools, prompt treatment ,and improved personal protection and vector control .
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.
Epidemio …Endemicity : defined by parasitemia rates or palpable spleen rates in children of 2-9yrs• Hypo endemic <10% X - low transmission, erratic/ focal, Protective immunity is not developed, all ages are symptomatic. Called unstable transmission. Mesoendemic 11-50% Hyper endemic 51-74% Holoendemic _>75%
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.
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 human bites/day/mosq. Logivity of vector (half life ) ----note; sporogony takes 8-30 days.
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)
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.
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 ind’l uponnext bite.Takes 8-30days to complete the sexual stage in mosquito.Note; human stage is asexual.
Transm … 2,blood transfusion ,by needle-stick injury(drug abusers),organ transplant_ ,congenital . Noincubation period in these modeof transmission and rare in occurance
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
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.
Pathog… +Cytoadherence----on venules and capillariesendothelium.+Rosetting------pf parasitized RBCS adherence on uninfected RBCs+Agglutination----on another parasitized RBCs
Pathog… NOTE; cytoadherence,rosetting,and agglutination arehallmerk of falciparum malaria pathogenesis ,result insequestration parasitizedRBCs into microcirculation,vital organs particularly brain ,placeta and result in severe diseases.
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
CM … clinical form : *non-falciparum /benign malaria *uncomplicated falciparum malaria *severe complicated malaria *chronic complication of malaria
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 Rx are important factors.
CM…..con’dClinical criteria for severity cerebral malaria –coma 30’ without any other c hypoglycemia acidosisAcute renal failure
Criteria for severity… Pulmonary edema/ARDS Severe anemia;NCNC ,thrombocytopenia,DIC ,(Thrombosis and bleeing) Liver injury Falciparum malaria in pregnancy
Chronic complication of malaria Hyperreactive malarial splenomegaly ; response to chronic/repeated infection Anemia , NCNCPresented with dragging LUQ abd pain& SSx of anemia
DIAGNOSIS OF MALARIA -clinical ,but no pathognomonic SSx of malaria -Light microscope : gold standard ,(Giemsa/Wright’s 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.
Dx… thin BF : thick BF : -other lab. Test : Hgb, periph morphology,RBS,RFT,LFT,Serum e ,LP & CSF analysis( if indicated).
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.
Rx-con’dUncomplicated 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
Uncomp falc mal Rx…B, 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.
Rx-con’d -severe complicated malaria :1,Quinine Iv ; loading 20mg/kg/4hrs in 5%DNS,then 12hrs later 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 12,24hrs then daily until pt take po.
Rx-con’d3- if no option ,quininedihydrochloride IM or artemether IM can be used.4-supportive treatment ; Rx hypoglycemia, anaemia, fever, coma care, … Chronic malaria :Chloquine for long duration , 6mosSplenectomy
PERVENTION ;Def ; control , elimination ,eradication, CONTROL :reduction of disease incidence and prevalence to levels that do not pose a threat to public , MDG 75% / 2015. Appropriate Rx, personal protection,vector control & vaccine ELIMINATION :reduction of incidence and transmission to zero in humans in a defined geographic area. ERADITION : global elimination of human disease .
Preven… CHALLENGES : -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 by non-immune travelers
REFERENCES : Harrison’s principles of internal medicine ,17th editon,2008 World health organization guidelines for the treatment of malaria,2nd edition ,2010 UpToDate17.3 Microbiology-ColouAtlas-2005.