Patogénesis de malaria by mohammed M .ppt

Patogénesis malaria

1. Pathogenesis of Malaria
By
Mohammed Mahmoud

2. Basic pathogenesis
Immunological
RBCs changes
Parasite itself

3. Immunopathogenesis
Immunity against Malaria is Premunition
immunity
Incompletereduce the severity of the attack
but not to prevention infection.
Takes several years to develop.
Fades away quickly.

4. Immunopathogenesis
APC
TH1
TH2 B-cell
Abs
Tc
NK
Mq
TNF
ROI
NO
Hum
CMI
IL1
IL1
IL2
IFNγ
IL4
IL5

5. Immunopathogenesis
TH1 produces IFN γ which activates the
macrophages to produce TNF, NO and
ROS which help to kill the parasite, on the
other hand, if these molecules are excessive
tissue damage will occur.

6. Immunopathogenesis
TH2 will produce IL4 & IL5activate the B
cells into plasma cells Abs which prevent
RBCs invasion by the parasite, on the other hand,
if excessive Abs produces Ag/Ab complex
which deposit in tissue activate complement
tissue damage, also Ag/Ab complexes stimulate
the macrophage to release their products more
tissue damage

7. RBCs changes
Cytoadherance and sequestration:
Rosetting

8. RBCs changes
Cytoadherance and sequestration
Rosetting
Deformability

9. Clinical picture
Complicated Malaria (P.falciparum)
Uncomplicated Malaria (other forms)

10. Uncomplicated Malaria
Fever:
Periodicity:
Every 3
rd
dayP.ovale, P. Vivax
Every 4
th
dayP. Malarie
Irregular P. Falciparum
Classical stages:
Cold stage
Hot stage
Sweating stage
Pathogenesis:
Mediated by host cytokines IL1, IL6, TNF

11. Uncomplicated Malaria
Anaemia:
Haemolysis of parasitized RBCs
BM suppression by IL1
Splenomegly:
Due to RE hyperplasia
Jaundice:
Due to haemlysis

12. Uncomplicated Malaria
Fate of the unttt acute attack:
Relapse: in case of P.vivax and ovale due to
activation of the dormant hypnozoites in the
liver.
Recrudescence: in case of P. Malarie and
falciparum due to persistance of small
number of the parasites in the blood.

13. Complicated Malaria
MetabolicAcidosis, Anaemia,
Hypoglycemia
CNSCerebral Malaria
CVSAlgid Malaria
LungARDS

14. Complicated Malaria
GITVomiting, diarrhea, abdominal pain
Liverhepatic failure
GBPigmented stone
SpleenTSS, rupture spleen
KidneysBlack water fever, ARF,
nephrosis
Obstetric

15. Metabolic
Acidosis:
Due to tissue anoxialactic acidosis
Tissue anoxia due to
RBCs changes
Severe anemia
Hypotension (Algid malaria)
Anemia
More in children and pregnant women
Caused by:
Haemolysis
BM suppresion by IL1
Autoimmune: Ab formed against parasited RBCs cross react
with unparasitized RBCs
2ry hyersplenism

16. Metabolic
Hypoglycaemia:
More in children and pregnant women
Due to:
Increase consumption of glucose by:
Parasites
Host after quinine therapy which stimulates B cells of the
pancreas
Decrease production of glucose by the liver due to cytokines
mediated suppresion of gluconeogenesis.

17. Cerebral Malaria
Diffuse disturbance of cerebral function
characterized by altered consciousness
commonly accompanied by convulsions in
presence of peripheral parasitaemia after
exclusion of other causes of
encephalopathy.

18. Cerebral malaria
Pathogenesis:
RBCs changes occlusion of the cerebral
mirocirculation.
Immunological, excessive release of cytokines from
the host cells e.g. macrophages
TNFα++ granulocytes to release their enzymes and ROS
Enhance expression of adhesion molecules on the
vascular endothelium promote cytoadherance
++ NO production (inhibitory neurotransmittor)

19. Algid Malaria
Malaria with peripheral circulatory
collapse and shock due to 2ry bacterial
infection likely UTI and pneumonia (due to
decreased immunity).

20. ARDS
Characterized by fever, respiratory distress,
hypoxemia inspite of supplemental oxygen
Caused by
Immunological e.g. TNF
RBCs changes
Lung infection 2ry to decrease immunity

21. GIT, Liver and GB
GITvomiting, watery diarrhea &
abdominal pain due to sequestration of
parasitized RBCs in intestinal
microcirculation.
Liver hepatic failure due to
sequestration of parasitized RBCs in
hepatic sinusoids
GB Pigmented stones 2ry to haemolysis.

22. Spleen
Tropical splenomegly syndrome (hyperactive
malarial splenomegly):
Gross splenomegly, hypersplenism and polyclonal B
lymphocyte proliferation excessive high IgM level
and raised titer of Ab against the present species of
parasite.
It is due to persistant malaria induced IgM
lymphocytotoxic Ab against T suppressor cell 
umcontrolled polyclonal proliferation of B cells.

23. Kidney
Black water fever:
More in children and non immune adults
Characterized by fever, rigors, haemoglobinuria,
oliguria and even anuria.
Blood film is usually negative or scanty parasites
Caused by massive intravascular haemlysis results
from:
High level of parasitaemia (> 100.000/ cmm)
Insufficient and irregular ttt with quinine renders the
parasitized RBCs antigenic Ab against quinine-
parasitized RBCs complex damage of RBCs
haemolysis
Primaquine in patients with G6PD deficiency

24. Kidney
ARF due to sequestration of parasitized
RBCs in the renal vessels.
Quartan Malarial nephropathy:
Intractable nephrotic syndrome with non
selective protinuria
Bad prognosis with no respose to steroids or
antimalarial
Caused by immune complex deposition

25. Obstetric
Pregnancy increase the parasitaemia which can
lead to:
Anemia
Low birth weight (packing of the placenta by the
parasitized RBCs)
Congenital infection:
Occur in non-immune pregnant
More in P.vivax than falciparum
Infants present with fever, haemolytic anemia and failure to
thrive.