MALARIA VISHNU NARAYAN .MR 2nd MBBS STUDENT TRAVANCORE MEDICAL COLLEGE KOLLAM KERALA INDIAMalaria is a mosquito-borne infectious disease of humans and other animals caused by protists ofthe genus Plasmodium, transmitted by the bite of female anopheles mosquito. Malaria is the mostimportant parasitic disease being widespread in tropical and subtropical regions in a broad bandaround the equator, including much of Sub-Saharan Africa, Asia, and the Americas.MALARIAL PARASITES OF MAN1. Plasmodium vivax – benign tertian/vivax malaria2. Plasmodium falciparum – malignant tertian/falciparum malaria3. Plasmodium ovale – ovale tertian malaria4. Plasmodium malariae – quartan malariaLIFE CYCLE 1. Human cycle-Shizogony Starts with introduction of sporozoites by the bite of an infected female anopheles mosquito 4 stages A) PRE-ERYTHROCYTIC SHIZOGONY Developmental phase inside the tissue of man Site-parenchyma cells of liver Consists of single generation of pre erythrocytic schizont which liberates merozoites Duration -- P.vivax-8 days P.ovale-9 days P.falciparum-6 days P.malariae-15days Cryptozoites—liberated merozoites- 2 types
i)micromerozoites – enter circulation ii)macromerozoites—re-enter liver cells No clinical manifestations or pathological damage Blood-sterileB) ERYTHROCYTIC SCHIZOGONY Site- within the RBCs Asexual reproduction giving rise to trophozoites shizont merozoites Asexual forms demonstrated in thick smears of peripheral blood 3 to 4 days after completion of pre-erythrocytic shizogony Duration—48 to 72 hours Parasitic multiplication bring out clinical attacks of malaria Cycle continued for considerable period but dies out due to exhaustion of asexual reproductive capacities and spontaneous destruction of parasitesC) GAMETOGENY After many cycles of erythrocytic shizogony Some merozoites give rise to GAMETOCYTES,capable of sexual reproduction after leaving human host Develop in RBCs of the capillaries of internal organs Mature gametocytes are seen in peripheral blood Duration of maturation- 4 days No febrile reactions Carrier- individual harbouring gametocytes(at least 12 /mm3 of blood, female gametocytes>male gametocytes)D) LATENT STAGE HYPNOZOITE STAGE Only in Vivax and ovale Arises from the initial tissue phase, capable of developing merozoites Responsible for relapses of vivax and ovale2) Mosquito cycle – SPOROGONY Sexual cycle of malarial parasite Gametocytes from human carriers transmitted to female anopheles mosquito during blood meal Inside the midgut,macrogametocytes give rise to a single macrogamete lacking a flagella while microgametocyte give rise to 4 -8 thread like,filamentous,flagellated microgametes
Microgamete moves towards the macrogamete and fertilisation occur by fusion of pronuclei resulting in a zygote. Fertilisation occurs within 20min-2 hours after mosquito blood meal Zygote lengthens and matures into ookinete within next 24 hours Ookinete is then engulfed by the mucosal cell while passing through the gut wall – transinvasion,and finally rests against external border of cell and basement membrane. Within the cells,ookinete develops into oocyst Oocyst-spherical mass surrounded by structure less capsule with single vesicular nucleus and pigment granules of macrogamete On maturation oocyst undergoes mitotic and meiotic divisions forming haploid sporozoites which are liberated into the insect’s haemocele by rupture of oocyst(on complete maturation-by 10th day of infection) Sporozoites are then transferred to different tissues and organs with a special predilection on salivary glands,maximum in ducts Sporozoites are the infective form, transmitted to humans by single bite of infected female anopheles mosquitoMOSQUITO HUMAN EXOERYTHROCYTIC SHIZOGONY(hepatocytes) Sporozoite Mosquito bite Hepatic shizont Hypnozoites (salivary duct) oocyst(mid gut wall) ERYTHROCYTIC SHIZOGONY(RBCs) Merozoites Trophozoite ookinete Schizont GAMEOGONY Zygote Gamete Blood meal Gametocytes (microgamete,megagamete) (microgametocyte,megagametocyte)FERTILISATION(midgut)
MORPHOLOGYFEATURE P.VIVAX P.MALARIAE P.FALCIPARUM P.OVALEInfected RBCs Enlarged,pale,fine Not enlarged,no Not enlarged,coarse Enlarged,oval,fimbr stippling(schuffner’s stippling,primarly stippling-Maurer’s iated dots)primarly invade invades older clefts,invades all RBCs,pale,conspico reticulocytes,young RBCs,Ziemann’s dots RBCs us James dots RBCs on prolonged stainingRing stage Large rings (1/3–1/2 red Large rings (1/3 red Small rings (1/5 red Large rings (1/3 redtrophozoites cell diameter). Usually cell diameter). Usually cell diameter). Often cell diameter). one chromatin granule; one chromatin two granules; Usually one ring delicate. granule; ring thick. multiple infections chromatin granule; common; ring ring thick. delicate, may adhere to red cells.Pigment in Fine; light brown; Coarse; dark brown; Coarse; black; few Coarse; darkdeveloping scattered. scattered clumps; clumps. yellow-brown;trophozoites abundant. scattered.Older Very pleomorphic. Occasional band Compact and Compact andtrophozoites forms. rounded. rounded.Mature More than 12 Fewer than 12 large Usually more than 12 Fewer than 12schizonts merozoites (14–24). merozoites (6–12). merozoites (8–32). large merozoites(segmenters) Often in rosette. Very rare in (6–12). Often in peripheral blood. rosette.Gametocytes Round or oval. Round or oval. Crescentic. Round or oval. PATHOGENECITY Mode of infection-inoculative method Transmitting agent-bite of infected female anopheles mosquito
Infective forms-sporozoites Portal of entry-skin Site of localisation-first in hepatocytes, then RBCs Incubation period-18days to 6 weeks –P.Malariae 10-14 days-othersPATHOLOGY During erythrocytic shizogony, the parasites produce a malarial pigment-haematin from haemoglobin. On completion of shizogony, along with merozoites haematin and other malarial toxins are also released which contribute to the fever The pigments are filtered out by cells of RES.So organs rich in RE cells become densely pigmented and there will be associated hyperplasia of RES,especially spleen and liver. Capillaries of internal organs-filled with parasitized red cells Vascular changes-congestion and dilatation of sinusoidal vessels Perivascular haemorrhages-in falciparum malaria Degenerative changes of parenchyma cells-due to hypoxia from capillary blockage Immunosuppression leading to secondary bacterial invasion.CLINICAL FEATURESPlasmodium vivax – benign tertian/vivax malariaPlasmodium falciparum – malignant tertian/falciparum malaria, pernicious malaria, Black water feverPlasmodium ovale – ovale tertian malariaPlasmodium malariae – quartan malaria1. FEBRILE PAROXYSMS- periodic episodes of fever alternating with symptom-freeperiods 3 Stages- 1.cold stage-sensation of cold, shivering (20min-1 hour) 2. Hot stage -fever, headaches, vomiting; seizures in young children (1-4hours) 3. Sweating stage - sweats, return to normal temperature, tiredness (2-3 hours) Tertian fever-48hour cycle with fever recurring every 3rd day Quartan fever-72hourcycle with fever recurring every 4th day Quotidian fever-fever recur every 24 hours-in Vivax/malariae Falciparum malaria may not show the febrile paroxysm.Instead,continuous or remittent fever is seen.
2. ANAEMIA- Microcytic or normocytic hypochromic type Associated increase in leucocytes initially; but as fever recurs,mild to moderate leukopenia is seen3. SPLENOMEGALYRELAPSES IN MALARIA Renewed clinical manifestation or parasitemia True relapse/recurrence-due to persistence of hypnozoites in liver,only in Vivax and ovale Recrudescence-due to persistent blood infection, feature of FalciparumPERNICIOUS MALARIA Series of phenomena occurring during the course of falciparum infection ,fatal if untreated 3 clinical subtypes 1. CEREBRAL MALARIA-hyperpyrexia,coma,paralysis 2. ALGID MALARIA-cold,clammy skin with vascular collapse and peripheral circulatory failure 3. SEPTICAEMIC MALARIA-high continued temperature,bilious remittent fever,pneumonia,cardiac syncopeBLACKWATER FEVER A manifestation of falciparum malaria occurring in previously infected subjects and inadequate treatment with quinine Pathogenesis-intravascular haemolysis due to antierythrocyte antibodies leading to methemoglobinemia,hemoglobinuria,hyperbilirubinaemia Clinical features-fever,rigor,bilious vomiting and prostration,jaundice with passage of dark red or blackish urine, a/c renal failure Treatment-chloroquine,blood transfusion,symptomatic treatmentLAB DIAGNOSIS Microscopic examination of Blood film –thick/thin film stained with Giemsa Antigen capture tests-chromatographic methods to detect a trophozoite derived protein in lysed blood-rapid diagnostic test(dip stick/test strip test) Serological tests-Immunofluorescence test, gel precipitation test,ELISA,IHA PCR Cultural examination Blood count Sternal puncture
TREATMENT 1. Essentially therapeutic Clinical cure-4 aminoquinolines Radical cure-primaquine 2. Protective Dihydrofolate reductase inhibitors-proguanil,trimethoprim 3. Synergists Sulphonamides,dapsonePROPHYLAXIS 1. Personal prophylaxis-protection against mosquito bites,chemoprophylaxis 2. Community prophylaxis-prevention of carriers,mosquito control measures Our Medical education system faces several challenges ultimately it is important to train our Medical students to be better future physicians, We have taken the STUDENT EMPOWERING PROJECT AT DEPARTMENT OF MICROBIOLOGY, TRAVANCORE MEDICAL COLLEGE, KOLLAM 691581 India to train the students in learning and practice of Medicine to the changing needs of the Society. Every student expresses the knowledge in different ways; we will be posting topics of interest to the wider section of the Medical students in the developing world, in writing essays which are made with their learning capabilities. Dr.T.V.Rao MD Professor of Microbiology