![Page 1: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/1.jpg)
MALARIA• 40% of the world’s population lives in
endemic areas• 3-500 million clinical cases per year• 1.5-2.7 million deaths (90% Africa)• increasing problem (re-emerging disease)
• resurgence in some areas• drug resistance ( mortality)
• P. falciparum• P. vivax• P. malariae• P. ovale
• causative agent = Plasmodium species• protozoan parasite• member of Apicomplexa• 4 species infecting humans
• transmitted by anopholine mosquitoes
![Page 2: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/2.jpg)
Life Cycle• sporozoites injected during
mosquito feeding• invade liver cells• exoerythrocytic schizogony
(merozoites)• merozoites invade RBCs• repeated erythrocytic
schizogony• gametocytes infective for
mosquito• fusion of gametes in gut• sporogony on gut wall in
hemocoel• sporozoites invade salivary
glands
![Page 3: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/3.jpg)
Anopheles
Transmission• sporozoites injected with saliva
• enter circulation• trapped by liver (receptor-ligand)
![Page 4: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/4.jpg)
Exoerythrocytic Schizogony• hepatocyte invasion• asexual replication• 6-15 days• 1000-10,000 merozoites• no overt pathology
![Page 5: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/5.jpg)
Hyponozoite Forms• some EE forms exhibit delayed
replication (ie, dormant)• merozoites produced weeks-to-
months after initial infection• only P. vivax and P. ovale
relapse = hypnozoite
recrudescence = subpatentt
![Page 6: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/6.jpg)
Erythrocytic Schizogony
• intracellular parasite undergoes trophic phase
• young trophozoite called ‘ring form’
• ingests host hemoglobin• cytostome• food vacuole• hemozoin (malarial pigment)
![Page 7: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/7.jpg)
Erythrocytic Schizogony
• nuclear division = begin schizont stage
• 6-40 nuclei• budding merozoites =
segmenter• erythrocyte rupture
releases merozoites
![Page 8: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/8.jpg)
Clinical Features• characterized by acute febrile attacks
(malaria paroxysms)• periodic episodes of fever alternating with
symptom-free periods• manifestations and severity depend on
species and host status• immunity, general health, nutritional state,
genetics• recrudescences and relapses can occur
over months or years• can develop severe complications
(especially P. falciparum)
![Page 9: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/9.jpg)
• paroxysms associated with synchrony of merozoite release
• between paroxysms temper-ature is normal and patient feels well
• falciparum may not exhibit classic paroxysms (continuous fever)
Malaria Paroxysm
tertian malariaquartan malaria
![Page 10: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/10.jpg)
Disease Severity Pv Po Pm Pf Paroxysm Severity
moderate to severe
mild mild to
moderate severe
Average (per mm3)
20,000 9,000 6,000 50,000-500,000
Maximum (per mm3)
50,000 30,000 20,000 2,500,000
Anemia ++ + ++ ++++ Duration
Disease Infection
3-8 w 5-8 y*
2-3 w 12-20 m*
3-24 w >20 y
2-3 w 6-17 m
Complications renal cerebral**
*true relapses ( recrudescence) due to dormant hypnozoite stage in liver **plus many other organs
![Page 11: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/11.jpg)
gametocytes
erythrocytic schizogony• 48 hr in Pf, Pv, Po• 72 hr in Pm
![Page 12: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/12.jpg)
Gametocytogenesis• alternative to asexual replication• induction factors not known
• drug treatment #'s• immune response #'s
• ring gametocyte• Pf : ~10 days• others: ~same as schizogony
• sexual dimorphism• microgametocytes• macrogametocytes
• no pathology• infective stage for mosquito
![Page 13: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/13.jpg)
Gametogenesis
• occurs in mosquito gut• ‘exflagellation’ most
obvious• 3X nuclear replication• 8 microgametes formed
• exposure to air induces temperature (2-3oC) pH (8-8.3)• result of pCO2
• gametoctye activating factor in mosquito• xanthurenic acid
![Page 14: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/14.jpg)
Sporogony• occurs in mosquito (9-21 d)• fusion of micro- and macrogametes
• zygote ookinete (~24 hr)• ookinete transverses gut epithelium ('trans-invasion')
![Page 15: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/15.jpg)
Sporogony• ookinete oocyst
• between epithelium and basal lamina
• asexual replication sporozoites
• sporozoites released
![Page 16: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/16.jpg)
Sporogony• sporozoites migrate
through hemocoel• sporozoites 'invade'
salivary glands
![Page 17: MALARIA 40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem](https://reader033.vdocuments.net/reader033/viewer/2022050920/551568d355034691418b4daa/html5/thumbnails/17.jpg)
Invasive Stages
Merozoite• erythrocytesSporozoite• salivary glands• hepatocytesOokinete• epithelium