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Aetiology
                     Management and Science University
                        International Medical School                  • Mosquito transmitted Disease
                                                                        Female Anopheles mosquito
                                   MBBS YEAR II

                                H & L System Module                   •       Caused by –
                             Lecture 16 : MALARIA                     -       Plasmodium vivax – beningn tertian malaria
                                                                      -       Plasmodium falciparum – malignant tertian malaria
                                                                      -       Plasmodium ovale – ovale tertian malaria
               DR.DURGADAS                        Date : 19/12/2012   -       Plasmodium malariae – quartan malaria




          Plasmodium knowlesi
                                                                                                  Malaria
                                                                          •    World wide 300-500 million cases/year
          - Autochthonous (native) cases have been                        •    And 1-3 million deaths (most 6 months – 3 years)
            documented in Malaysia, Thailand, Myanmar,                    •    Pl.falciparum accounts for 95 % of deaths
            Singapore, the Philippines,                                   •    HIV and Malaria co infection is common in some area
            and other neighboring countries.                                   and takes severe form
                                                                          •    P.vivax and P.ovale cause latent infection because of
          - Present in Monkey and can cause malaria in humans                  hypnozoite (slow growing parasite) in liver cells
                                                                          •    Malaria in first trimester of pregancy (P.falciparum)
          - Morphology similar to P.malariae                                   results in severe anaemia, complications include
                                                                               miscarriage
                                                                          •    Fetal complications include low birth weight,
                                                                               premature birth, death)
                                                                          •    Mixed infection P.v/P.f/P.o (~2-5%)




            Life cycle involves two hosts –
                                                                              Life cycle
            1. Humans – Intermediate host
            2. Female Anopheles Mosquito – Definitive host
                                                                              Schizogony
            1. Schizogony – asexual reproduction of parasite
               (In Humans –Schizogony occurs in
               Liver cells –Exoerythrocytic schizogony and
               RBCS – Erythrocytic schizogony)
                                                                                                               Gametogony
            2. Gametogony – Production of Male and Female
               gametocytes (Mosquito)

            3. Sporogony – Production of sporozoites(Mosquito)
                                                                              Sporogony




                                                                                                                                       1
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Morphological forms

             1. Schizogony (in Humans)
               a. Trophozoite – Early (ring form), Late (amoeboid form)
               b. Schizont – Early (Only nuclei), Late (with merozoites)
               c. Merozoites

             2. Gametogony (In mosquito)
                a. Gametocytes forming cells
                b. Gametocytes – Male, Female

             3. Sporogony (In Mosquito)
                a. Zygote
                b. Ookinete
                c. Oocyst
                d. Sporozoites




                                                                                               2
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P.vivax, P.ovale – Hypnozoites
                                  Slow growing parasites-
                                  Responsible for relapse




                                                                      Complications in P.falciparum malaria –
                Pathogenicity/Clinical manifestations
                                                                     Heavy parasitized RBCs (>5%)become deformed, sticky, and
            P.vivax, P.falciparum, P.ovale, P.malariae, P.knowlesi   adhere to endothelium of capillaries in internal organs.-
                                                                     Results in vascular damage and vascular obstruction.
         • Malaria –        Febrile paroxysm (8-12 hours)
           consists of cold stage, hot stage and profuse sweating.   1. Cerebral malaria - Haemorrhage & Necrosis.
           Typical picture is typical bouts of fever with rigors
           followed by Anaemia and Spleenomegaly.                    2. Black water fever –extensive haemolysis, Kidney damage
         • Anaemia – destruction of RBCs by parasite and                                   haemoglobinuria, with Hb pigments
                                                                                           black colour urine –renal failure
           autoantibodies
         • Associated symptoms – Severe headache, nausea,            3. Pernicious anaemia – haemolytic
           vomiting, Fever – 41 degree Centigrade
                                                                     4. Septicemic malaria – involving many organs
                                                                                             Pulmonary edema – Lungs
                                                                     5. Hypoglycemia




                 Incubation Period –
                                                                            Merozoite induced Malaria
                 P.vivax & P.ovale : 10-14 days
                 P. falciparum : 8-12 days                           • Blood transfusion
                 P.malariae : 18-40 days
                                                                     • Congenital malaria
                 Malaria pigments – Residues of Haemoglobin
                                                                     • Shared syringes
                 (Haemozoin – toxic product)
                                                                     Disease is self limited as no exoerythrocytic schizogony
                 P. vivax – Numerous Golden brown pigments
                 P. falciparum – few black pigments
                 P.malariae – Numerous dark brown pigments
                 P.ovale – Numerous blackish brown pigments




                                                                                                                                 3
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Immunity :
                                                                                Laboratory Diagnosis
          Partial immunity. Antibodies block merozoites
          resulting in low level of Parasitemia and                     1. Microscopy :
          low grade symptoms – premunition.

          • Duffy blood group antigen is receptor for parasite.           Thick smear – detects genus
                                                                          Thin smear – detects species
          • Sickle red cells (abnormal Hb) donot
            support parasite growth
                                                                        Smear is stained by Leishman or Giemsa
          • Individuals deficient in G6PDH also resistant to malaria
                                                                        & examined for any of the morphological
          • Severe Malnutrition and iron deficiency gives protection     forms of Plasmodium
          against malaria




           Plasmodium falciparum
           with two chromatin dots


                                            Growing stages of P.f.




                                                                       P.falciparum gametocytes 27, 28 = Male and 29, 30 = Female

              Trophozoite                           P.f. Schizont




                       P.falciparum gametocytes
                         In stained blood smear



                                                                                                    P.vivax – Trophozoite -amoeboid
                                                                          P.vivax – Ring stage




                                                                                                      P.v. Gametocyte , 28,29 = Female
                                                                            P.v. Schizont                                 30 = male




                                                                                                                                         4
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2. Detection of Antibodies                              4. Species-specific PCR diagnosis of malaria
          • Used in screening blood donors
          • Suspected malaria with blood smear negative for parasite
                                                                                                Lane S: Molecular base pair standard
                                                                                                (50-bp ladder). Black arrows show the
                                                                                                size of standard bands.

                                                                                                Lane 1: band for P. vivax (size: 120 bp)

                                                                                                Lane 2: band for P. malariae (size:144 bp)

                                                                                                Lane 3: band for P. falciparum (size:205bp)

                                                                                                Lane 4: band for P. ovale (size: 800 bp)

                 Indirect immunoflourescence Test – Schizont

          3. Detection of Protein antigen of P.falciparum by ELISA




                          Malaria – Epidemiology
                                                                                 Prevention and Control
                                                                        • Personal prophylaxis – avoid mosquito bite,
                                                                          use bed nets, insect repellent applications on
                                                                          exposed skin.
                                                                        • Chemoprophylaxis to travellers visiting
                                                                          endemic countries
                                                                        • Control by – Mosquito breeding sites, use of
             • ~200 million cases of malaria worldwide                    insecticides.
             • ~1 million die of malaria every year
             • Increased cases of Choroquine resistant
               P.falciparum strains
             • Disease is endemic in many countries




                                                                       Q. 1. Write causative agents of Malaria
              Treatment – drugs in use
                                                                       Q.2. Define Schizogony, gametogony and sporogony

           • Chloroquine                                               Q.3. In Plasmodium parasite which one is intermediate host
                                                                           and Definitive host.
           • Primaquine
           • Combination of sulphadoxine &                             Q.4. Write life cycle of Plasmodim.
             pyrimethamine or mefloquine
                                                                       Q.5. Write morphological forms of parasite found in humans
           • Chinese Herbal drug – Artesunate
                                                                           that are diagnostic importance
           • In severe p.f. infection quinine
                                                                       Q.6. Name infective morphological form of Plasmodium

                                                                       Q.7. Write Pathogenicity of P.vivax

                                                                       Q.8. Write pathogenicity of P.falciparum & complications




                                                                                                                                              5
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Q.9. State the reason for severity of P.falciparum infection

         Q.10. Write laboratory diagnosis of malaria

         Q.11. How do you differentiate trophozoite and
               gametocytes of P.vivax and P.falciparum.

         Q.12. Write transmission mode – name Vector involved

         Q.13. What is merozoite induced malaria,
               Give two examples.

         Q.14. Why individuals who lack in duffy blood group
               antigen on RBCs are resistant to Malaria

         Q.15. Why malaria eradication is difficult.
               Give two reasons
                  ------------------------------------------------------




                                                                                               6
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4.malaria

  • 1. Aetiology Management and Science University International Medical School • Mosquito transmitted Disease Female Anopheles mosquito MBBS YEAR II H & L System Module • Caused by – Lecture 16 : MALARIA - Plasmodium vivax – beningn tertian malaria - Plasmodium falciparum – malignant tertian malaria - Plasmodium ovale – ovale tertian malaria DR.DURGADAS Date : 19/12/2012 - Plasmodium malariae – quartan malaria Plasmodium knowlesi Malaria • World wide 300-500 million cases/year - Autochthonous (native) cases have been • And 1-3 million deaths (most 6 months – 3 years) documented in Malaysia, Thailand, Myanmar, • Pl.falciparum accounts for 95 % of deaths Singapore, the Philippines, • HIV and Malaria co infection is common in some area and other neighboring countries. and takes severe form • P.vivax and P.ovale cause latent infection because of - Present in Monkey and can cause malaria in humans hypnozoite (slow growing parasite) in liver cells • Malaria in first trimester of pregancy (P.falciparum) - Morphology similar to P.malariae results in severe anaemia, complications include miscarriage • Fetal complications include low birth weight, premature birth, death) • Mixed infection P.v/P.f/P.o (~2-5%) Life cycle involves two hosts – Life cycle 1. Humans – Intermediate host 2. Female Anopheles Mosquito – Definitive host Schizogony 1. Schizogony – asexual reproduction of parasite (In Humans –Schizogony occurs in Liver cells –Exoerythrocytic schizogony and RBCS – Erythrocytic schizogony) Gametogony 2. Gametogony – Production of Male and Female gametocytes (Mosquito) 3. Sporogony – Production of sporozoites(Mosquito) Sporogony 1 Create PDF files without this message by purchasing novaPDF printer (http://www.novapdf.com)
  • 2. Morphological forms 1. Schizogony (in Humans) a. Trophozoite – Early (ring form), Late (amoeboid form) b. Schizont – Early (Only nuclei), Late (with merozoites) c. Merozoites 2. Gametogony (In mosquito) a. Gametocytes forming cells b. Gametocytes – Male, Female 3. Sporogony (In Mosquito) a. Zygote b. Ookinete c. Oocyst d. Sporozoites 2 Create PDF files without this message by purchasing novaPDF printer (http://www.novapdf.com)
  • 3. P.vivax, P.ovale – Hypnozoites Slow growing parasites- Responsible for relapse Complications in P.falciparum malaria – Pathogenicity/Clinical manifestations Heavy parasitized RBCs (>5%)become deformed, sticky, and P.vivax, P.falciparum, P.ovale, P.malariae, P.knowlesi adhere to endothelium of capillaries in internal organs.- Results in vascular damage and vascular obstruction. • Malaria – Febrile paroxysm (8-12 hours) consists of cold stage, hot stage and profuse sweating. 1. Cerebral malaria - Haemorrhage & Necrosis. Typical picture is typical bouts of fever with rigors followed by Anaemia and Spleenomegaly. 2. Black water fever –extensive haemolysis, Kidney damage • Anaemia – destruction of RBCs by parasite and haemoglobinuria, with Hb pigments black colour urine –renal failure autoantibodies • Associated symptoms – Severe headache, nausea, 3. Pernicious anaemia – haemolytic vomiting, Fever – 41 degree Centigrade 4. Septicemic malaria – involving many organs Pulmonary edema – Lungs 5. Hypoglycemia Incubation Period – Merozoite induced Malaria P.vivax & P.ovale : 10-14 days P. falciparum : 8-12 days • Blood transfusion P.malariae : 18-40 days • Congenital malaria Malaria pigments – Residues of Haemoglobin • Shared syringes (Haemozoin – toxic product) Disease is self limited as no exoerythrocytic schizogony P. vivax – Numerous Golden brown pigments P. falciparum – few black pigments P.malariae – Numerous dark brown pigments P.ovale – Numerous blackish brown pigments 3 Create PDF files without this message by purchasing novaPDF printer (http://www.novapdf.com)
  • 4. Immunity : Laboratory Diagnosis Partial immunity. Antibodies block merozoites resulting in low level of Parasitemia and 1. Microscopy : low grade symptoms – premunition. • Duffy blood group antigen is receptor for parasite. Thick smear – detects genus Thin smear – detects species • Sickle red cells (abnormal Hb) donot support parasite growth Smear is stained by Leishman or Giemsa • Individuals deficient in G6PDH also resistant to malaria & examined for any of the morphological • Severe Malnutrition and iron deficiency gives protection forms of Plasmodium against malaria Plasmodium falciparum with two chromatin dots Growing stages of P.f. P.falciparum gametocytes 27, 28 = Male and 29, 30 = Female Trophozoite P.f. Schizont P.falciparum gametocytes In stained blood smear P.vivax – Trophozoite -amoeboid P.vivax – Ring stage P.v. Gametocyte , 28,29 = Female P.v. Schizont 30 = male 4 Create PDF files without this message by purchasing novaPDF printer (http://www.novapdf.com)
  • 5. 2. Detection of Antibodies 4. Species-specific PCR diagnosis of malaria • Used in screening blood donors • Suspected malaria with blood smear negative for parasite Lane S: Molecular base pair standard (50-bp ladder). Black arrows show the size of standard bands. Lane 1: band for P. vivax (size: 120 bp) Lane 2: band for P. malariae (size:144 bp) Lane 3: band for P. falciparum (size:205bp) Lane 4: band for P. ovale (size: 800 bp) Indirect immunoflourescence Test – Schizont 3. Detection of Protein antigen of P.falciparum by ELISA Malaria – Epidemiology Prevention and Control • Personal prophylaxis – avoid mosquito bite, use bed nets, insect repellent applications on exposed skin. • Chemoprophylaxis to travellers visiting endemic countries • Control by – Mosquito breeding sites, use of • ~200 million cases of malaria worldwide insecticides. • ~1 million die of malaria every year • Increased cases of Choroquine resistant P.falciparum strains • Disease is endemic in many countries Q. 1. Write causative agents of Malaria Treatment – drugs in use Q.2. Define Schizogony, gametogony and sporogony • Chloroquine Q.3. In Plasmodium parasite which one is intermediate host and Definitive host. • Primaquine • Combination of sulphadoxine & Q.4. Write life cycle of Plasmodim. pyrimethamine or mefloquine Q.5. Write morphological forms of parasite found in humans • Chinese Herbal drug – Artesunate that are diagnostic importance • In severe p.f. infection quinine Q.6. Name infective morphological form of Plasmodium Q.7. Write Pathogenicity of P.vivax Q.8. Write pathogenicity of P.falciparum & complications 5 Create PDF files without this message by purchasing novaPDF printer (http://www.novapdf.com)
  • 6. Q.9. State the reason for severity of P.falciparum infection Q.10. Write laboratory diagnosis of malaria Q.11. How do you differentiate trophozoite and gametocytes of P.vivax and P.falciparum. Q.12. Write transmission mode – name Vector involved Q.13. What is merozoite induced malaria, Give two examples. Q.14. Why individuals who lack in duffy blood group antigen on RBCs are resistant to Malaria Q.15. Why malaria eradication is difficult. Give two reasons ------------------------------------------------------ 6 Create PDF files without this message by purchasing novaPDF printer (http://www.novapdf.com)