Malaria pathogenesis and reason for drug resistantance

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Malaria pathogenesis and reason for drug resistantance

  1. 1. Malaria Pathogenesis andReason for drug resistant
  2. 2. Plasmodium vivax (tertian)Plasmodium ovale (tertian)Plasmodium falciparum (tertian)Plasmodium malariae (quartian)
  3. 3. Malaria Life SporogonyCycle OocystLife Cycle Sporozoites Mosquito Salivary Zygote Gland Hypnozoites Exo- (for P. vivax and P. ovale) erythrocytic (hepatic) cycle Gametocytes Erythrocytic CycleSchizogony
  4. 4. Exo-erythrocytic (hepatic) Cycle: Sporozoires injected Sporozoites infect liver cells and into human host during develop into schizonts, which release blood meal merozoites into the bloodParasitesmature inmosquitomidgut and HUMAN Dormant liver stages MOSQUITO (hypnozoites) of P.migrate tosalivary vivax and P. ovaleglands Erythrocytic Cycle: Merozoites infect red blood cells to form Some merozoites schizonts Parasite undergoes sexual reproduction in differentiate into male or the mosquito female gametocyctes
  5. 5. Sporogonic cycle Infective Period Mosquito bites uninfected person Mosquito Vector Parasites visible Human HostMosquito bitesgametocytemic Prepatent Period Symptom onsetperson Recovery Incubation Period Clinical Illness
  6. 6.  Blood is infected with sporozoites about 30 minutes after the mosquito bite The sporozoites are eaten by macrophages or enter the liver cells where they multiply – pre-erythrocytic schizogeny P. vivax and P. ovale sporozoites form parasites in the liver called hypnozoites
  7. 7.  P. malariae or P. falciparum sporozoites do not form hypnozites, develop directly into pre-erythrocytic schizonts in the liver Pre-erythrocytic schizogeny takes 6-16 days post infection Schizonts rupture, releasing merozoites which invade red blood cells (RBC) in liver
  8. 8.  P. vivax and P. ovale hypnozoites remain dormant for months They develop and undergoes pre- erythrocytic sporogeny The schizonts rupture, releasing merozoites and produce clinical relapse
  9. 9. Malaria Life SporogonyCycle OocystLife Cycle Sporozoites Mosquito Salivary Zygote Gland Hypnozoites Exo- (for P. vivax and P. ovale) erythrocytic (hepatic) cycle Gametocytes Erythrocytic CycleSchizogony
  10. 10.  P. vivax and P. ovale hypnozoites remain dormant for months They develop and undergoes pre- erythrocytic sporogeny The schizonts rupture, releasing merozoites and producing clinical relapse
  11. 11.  Pre-patent period – interval between date of infection and detection of parasites in peripheral blood Incubation period – time between infection and first appearance of clinical symptoms Merozoites from liver invade peripheral (RBC) and develop causing changes in the RBC There is variability in all 3 of these features depending on species of malaria
  12. 12.  Trophozoites are early stages with ring form the youngest Tropohozoite nucleus and cytoplasm divide forming a schizont Segmentation of schizont’s nucleus and cytoplasm forms merozoites Schizogeny complete when schizont ruptures, releasing merozoites into blood stream, causing fever These are asexual forms
  13. 13.  Merozoites invade other RBCs and schizongeny is repeated Parasite density increases until host’s immune response slows it down Merozoites may develop into gametocytes, the sexual forms of the parasite
  14. 14.  Schizogenic periodicity is length of asexual erythrocytic phase  48 hours in P.f., P.v., and P.o. (tertian)  72 hours in P.m. (quartian) Initially may not see characteristic fever pattern if schizogeny not synchronous With synchrony, periods of fever or febrile paroxsyms assume a more definite 3 (tertian)- or 4 (quartian)- day pattern
  15. 15.  Drug resistance is the ability of the parasite species to survive and/or multiply despite the administration and absorption of a drug given in doses equal to or higher than those usually recommended but within the limit of tolerance.
  16. 16.  Longer half-life. Single mutation for resistance. Poor compliance Host immunity. Number of people using these drugs.
  17. 17.  a long terminal elimination half-life a shallow concentration-effect relationship mutations that confer marked reduction in susceptibility.
  18. 18.  Drug resistance is most commonly seen in P. falciparum. Only sporadic cases of resistance have been reported in vivax malaria. Resistance to chloroquine is most prevalent
  19. 19.  WHO has developed a simple scheme for estimating the degree of resistance that involves studying the parasitemia over 28 days. Smears on day 2, 7 and 28 are done to grade the resistance as R1 to R3. In a case of normal response parasite count to fall to 25% of pre- treatment value by 48 hours and smear should be negative by 7 days.
  20. 20.  The asexual parasite count reduces to 25% of the pre-treatment level in 48 hours after starting the treatment and complete clearance after 7 days, without subsequent recrudescence - Complete Recovery.
  21. 21.  The asexual parasitemia reduces to < 25% of pre-treatment level in 48 hours, but reappears between 2-4 weeks.
  22. 22.  The asexual parasitemia reduces to < 25% of pre-treatment level in 48 hours, but reappears earlier.
  23. 23.  Marked reduction in asexual parasitemia (decrease >25% but <75%) in 48 hours, without complete clearance in 7 days.
  24. 24.  Minimal reduction in asexual parasitemia, (decrease <25%) or an increase in parasitemia after 48 hours.
  25. 25.  1. In endemic areas it is not easy to differentiate recrudescence from re-infection. 2. Recrudescence can occur beyond 28 days also. 3. Therapeutic failure could be due to other causes also. 4. RII is a very broad category. 5. Practical difficulties in following the patient for 28 days. 6. Intermittent nature of parasitemia in the blood
  26. 26. Resistance develops most rapidly when a population of parasite encounters subtherapeutic concentration of antimalarial drugs..
  27. 27.  The following points will be helpful in reducing the emergence of resistance: Selection of drugs - Use conventional drugs first in uncomplicated cases. Greater the exposure, higher will be the emergence of resistance. Avoid drugs with longer half-life if possible Ensure compliance
  28. 28.  Avoid basic antimalarials for non-malarial indications (e.g. Chloroquine for rheumatoid arthritis in a malarial endemic area). Monitoring for resistance and early treatment of these cases to prevent their spread. Clear policy of using newer antimalarials. Use of combinations to inhibit emergence of resistance
  29. 29. THANK YOU

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