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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.
CONTENT-

 introduction                 1’
 Epidemiology                 5’
 Etiology and pathogenesis   10’
 Clinical manifestation      30’
 Diagnosis                    5’
 Treatment outline           3’
 Prevention                   5’
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.
Entomologic inoculation rate( EIR) :

number of infectious mosquito bite/person/yr.
Has seasonal / geographic difference.




 EIR <10/yr ---- low transmission
 EIR 10-49/yr---intermediate
 EIR _ >50/yr—high transmission area/stable transmission
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 ,host
Protozoa : 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 tissue


Arthropods : 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 gametocyteszygote(in the midgut)
ookinete
             penetrate gut wall
hemolymphsalivary glandsporozoite
(motile) through saliva inoculated into noninfectious ind’l upon
next 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 MALARIA


Inoculation 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.  
 RBCs change : - intracellular protien(Hgb) degraded,
 Cell membrane altered ; transport property ,
 Irregular shape , flexiblity lost,become antigenic

 Particularly, p. falciparum:
form ‘knobs’ =antigenic-variant ,which
  Helps as adhensive.
Pathog


 +Cytoadherence----on venules and capillaries
endothelium.

+Rosetting------pf parasitized RBCS adherence on
 uninfected RBCs

+Agglutination----on another parasitized RBCs
Pathog


 NOTE; cytoadherence,rosetting,and agglutination are
hallmerk of falciparum malaria pathogenesis ,result in
sequestration parasitizedRBCs into microcirculation
,vital organs particularly brain ,placeta and result in
  severe diseases.
    HOST RESPONSE ;

 Nonspecific defense involved(Abs-to
    sporozoite, 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
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.sp

p.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
 Clinical manifest. Con’d


 presentation        :non-falcip & uncomplicated falcip malaria

-early symptoms ---nonspecific;headache,vomiting,abd pain,diarrh
-classic --- paroxysms 0f fever spike,chills and rigors at regular

p.v / p.ov --------- tertian fever(q48hrs)
p.f ------------------malignant tertian fever
p.m ---------------quartan fever(q72hrs)
CM

 :severe complicated falciparum malaria

Def: 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’d

Clinical criteria for severity

 cerebral malaria –coma 30’ without any other c

 hypoglycemia

 acidosis

Acute 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 , NCNC


Presented 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’d
Uncomplicated falcip malaria,
   A, first line ,ACT for 3 days

1, 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 7days

1, atresunate + TTC or Doxycy. Or Clindamy
2, 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’d
3- 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 , 6mos
Splenectomy
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

THE   END !




THANK YOU !
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.

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Understanding Malaria Pathogenesis and Treatment

  • 1. 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.
  • 2. CONTENT-  introduction 1’  Epidemiology 5’  Etiology and pathogenesis 10’  Clinical manifestation 30’  Diagnosis 5’  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 sensitive diagnostic tools, prompt treatment ,and improved personal 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 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%
  • 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 <10/yr ---- low transmission  EIR 10-49/yr---intermediate  EIR _ >50/yr—high 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 human bites/day/mosq.  Logivity of vector (half life ) ----note; sporogony takes 8-30 days.
  • 10. ETIOLOGY  Parasites ---Greece word, mean in close association with another organism of different species ,host Protozoa : 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 tissue Arthropods : 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 gametocyteszygote(in the midgut) ookinete penetrate gut wall hemolymphsalivary glandsporozoite (motile) through saliva inoculated into noninfectious ind’l upon next 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 MALARIA Inoculation 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.
  • 17.  RBCs change : - intracellular protien(Hgb) degraded, Cell membrane altered ; transport property , Irregular shape , flexiblity lost,become antigenic Particularly, p. falciparum: form ‘knobs’ =antigenic-variant ,which Helps as adhensive.
  • 18. Pathog
 +Cytoadherence----on venules and capillaries endothelium. +Rosetting------pf parasitized RBCS adherence on uninfected RBCs +Agglutination----on another parasitized RBCs
  • 19. Pathog
  NOTE; cytoadherence,rosetting,and agglutination are hallmerk of falciparum malaria pathogenesis ,result in sequestration parasitizedRBCs into microcirculation ,vital organs particularly brain ,placeta and result in severe diseases.
  • 20.  HOST RESPONSE ;  Nonspecific defense involved(Abs-to sporozoite, 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
  • 21. 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.sp p.f =6-16days ,p.v and p.ov =10-21days ,p.m=21-42d months,even yrs
  • 22. CM 
  clinical form : *non-falciparum /benign malaria *uncomplicated falciparum malaria *severe complicated malaria *chronic complication of malaria
  • 23.  Clinical manifest. Con’d  presentation :non-falcip & uncomplicated falcip malaria -early symptoms ---nonspecific;headache,vomiting,abd pain,diarrh -classic --- paroxysms 0f fever spike,chills and rigors at regular p.v / p.ov --------- tertian fever(q48hrs) p.f ------------------malignant tertian fever p.m ---------------quartan fever(q72hrs)
  • 24. CM
  :severe complicated falciparum malaria Def: 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.
  • 25. CM
..con’d Clinical criteria for severity  cerebral malaria –coma 30’ without any other c  hypoglycemia  acidosis Acute renal failure
  • 26. Criteria for severity
  Pulmonary edema/ARDS  Severe anemia;NCNC ,thrombocytopenia,DIC ,(Thrombosis and bleeing)  Liver injury  Falciparum malaria in pregnancy
  • 27. Chronic complication of malaria  Hyperreactive malarial splenomegaly ; response to chronic/repeated infection  Anemia , NCNC Presented with dragging LUQ abd pain& SSx of anemia
  • 28. 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.
  • 29. Dx
  thin BF :  thick BF :  -other lab. Test : Hgb, periph morphology,RBS,RFT,LFT,Serum e ,LP & CSF analysis( if indicated).
  • 30.
  • 31. 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.
  • 32. Rx-con’d Uncomplicated falcip malaria, A, first line ,ACT for 3 days 1, artemether-lumefantrine(coartem20/120) 2, artesunate-amodiaquine(100/270) 3, artesunate-mefloquine(50/250) 4, atresunate-sufadoxina/pyrimethamine(50-500/25) 5, dihydroartemisinin-piperaquine
  • 33. Uncomp falc mal Rx
 B, second line ,for 7days 1, atresunate + TTC or Doxycy. Or Clindamy 2, Quinine + TTC or Doxycy. Or Clindamy  Pregnant- quinine + Clindamy/7d  Lactating –all except primaqu,TTC&Doxycy.
  • 34. 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.
  • 35. Rx-con’d 3- 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 , 6mos Splenectomy
  • 36. 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 .
  • 37. 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 
  • 38. THE END ! THANK YOU !
  • 39. 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.