FALCIPARUM MALARIA AN OVER VIEW

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FALCIPARUM MALARIA AN OVER VIEW

• DR.C.K.TALUKDAR
• 
  MD.,DRM,FICP,FICN,FICC
• PRAGATI NURSING HOME
• NALBARI

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MALARIA Basic
considerations and clinical features Malaria
in man is caused by four distinct
speciesofmalaria parasite P.vivax,P.falciparum,
P.malariae,P.ovale P.Vivax P.falciparum are
resposible for most of the infections found
throughout the malarial belt.P.malariae is
widely distributed but is less common.P.ovale
is rare but in West Africa it seems to have
replaced P.vivax.Malaria is estimated to kill
between 1.5 and 2.7 millionpeople each year.In
an average one person, often a child below 5yrs.
Of age die in every 12 seconds.Additional
300-500 million people contact the disease each
year(Butlon,1997)
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MALARIA MILESTONES

• 1600 B.C. References can be found in the
  writings
• 400 Hippocrates description of
  malaria.Charaka
• and Sushrutha gave vivid
  descriptions of malaria
• even associated it with the
  bites of the mosquitoes.
• 1640 A.D. Huan del Vego Cinchona bark for
  malaria treatment
• 1696 Morton first detailed picture of
  Malaria.
• 1717 Lanicsi Links malaria to bad air in
  swamps and thus
• originates the name malaria.
  
  
  
  
  
• 1816 Gize-Extraction of quinine from
  cinchona bark
• 1820 Pelletier and Caventou extraction
  of pure quinine alkaloids
• 1880 Laveran identifies malarial
  parasite under microscope.
• 1895 Golgi-Identification of P.vivax
  P.malariae
• 1889-90 Sakharov,Marchiafava,Celli-identificat
  ion of P.falciparum
• 
  
  cont.

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1897 Ronald RossDemonstration on malarial
oocysts in gut of female anopheles
mosquito

• 1934 Chloroquine synthesized by Germans.
  
  
  
• 1939 Paul Miller Insecticidal properties of
  DDT
• 1944 Curd, Davey, Rose Synthesis of
  Proguanil for treatment.
• 1950 Elderfield Synthesis of primaquine.
• 1967 WHO- emphasis on control of malaria
  rather than global eradication of the disease.
• 1990s Synthesis of quinine analogue
  mefloquine.
  Artemesinins obtained from Quinghaosu
  introduced for resistant malaria.
• 1994 Sequencing of P.Falciparum Genome begun
  
• 1999 WHO Recommends Combined therapy to
  delay resistance development to anti-malarials
• Including Artemesinin.
• 2000 Chloroquine resistance gene identified
  as PfeRTK767

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PLASMODIUM VIVAX1. Red cells containing
parasites are usually enlarged.2. Schuffners
dots are frequently present in the red cells as
shown.3. The mature ring forms tend to be large
and coarse.4. Developing forms are frequently
present.

• PLASMODIUM FALCIPARUM
• 1. Red cells are not enlarged.
• 2. Rings appear fine and delicate there maybe
• several in one cell.
• 3. It is unusual to see developing forms in
  peripheral
• blood films.
• 4. Gametocytes have a characteristic crescent
• shape appearance.

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PLASMODIUM MALARIAE1.Ring forms may have a
squarish appearance. 2.Band forms are a
characteristic of this species. 3.Mature
schizonts may have a typical daisy head
appearance with up to ten merozoites.

• PLASMODIUM OVALE
• 1. Only found in Africa.
• 2. Red cells enlarged.
• 3. Comet forms common.
• 4. Rings large and coarser.

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MALARIA PATHOLOGY Pigmentation of various
organs with haemozoin giving a characteristic
SLATE GREY Or BLACK COLOUR. Hyperplasia
of the Reticulo-Endothelial system resulting from
increased activity in order to deal with parasite
and their product. Parasitized erythrocytes
filling the Lumina of the capillaries of the
internal organs. This is particularly seen in
P.falciparum infection. Vascular
changes-dilatation of sinusoidal vessels,
perivascular haemorrhages are seen in falciparum
malaria. Degenerative changes of parenchyma
cells due to hypoxia seen in falciparum
malaria. Effects of anaemia.
Immunosupression has been observed in malarial
infection and this may lead to secondary
bacterial infection.
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THE SPLEENSpleen is enlarged,colour varies from
slate gray to black, capsule is thin stretched,
consistency soft in acute cases while firm in
chronic cases. AGUE CAKE SPLEEN THE
LIVERThe Liver is uniformly enlarged due to
vascular congestion and proliferation of
reticuloendothelial cells. The colour varies from
chocolate red to slate gray or even black
depending upon the stage of congestion and
deposition of the haemozoin pigment.BONE
MARROWKIDNEYS
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Does the Patient Need Hospitalization ?
Seriously ill patients needing Hospitalization-
Include- Continuous vomiting andinability
to retain oval drugs. Increasing Headache.
Severe Dehydration. Poor general
condition. Alteration of sensorium.
Suspected cerebral malaria with unarousable
Coma. Hyper pyrexia, convulsion.
Pregnancy Oedema. Bleeding disorders.
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COMPLICATIONS Cerebral malaria and
coma.Hyperpyrexia.Haemolytic Anaemia.Non
cardiogenic pulmonary oedema (ARDS ) Acute
tubular necrosis and renal failure Acute
Hepatomegaly and centrilobular necrosis
Hypoglycaemia An adrenal insufficiency like
syndrome Cardiac dysrhythmias Lactic acidosis
.
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Pathophysiology of complicated malaria

• Pathology associated with all malarial species is
  related to the rupture of the infected RBC and
  release of haemozoin
• (Malarial pigment).
• An increased in reticulo-endothelial system is
  fond causing hepato-splenomegaly.
• Cytoadhence of infected red cells to the vascular
  endothelium RBCs causing rossetting-compromises
  microcirculatory flow.
• In cerebral malaria-due to sequestration of the
  infected
• erythrocyles in the cerebral microcirculation.
• Sequestration in cytiadherence of trophozoite and
  schizont infected erythrocytes to the endothelial
  cells of the deeper vascular beds of the vital
  organs-specially the brain,liver,gut,heart
  placenta,

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Table 1 Anti-malarial Drug
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Contd.Table 1- Anti-malarial Drugs
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Contd.
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Contd.
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Treatment of Resistant Malaria
(Uncomplicated Resistant)

• 1.Sulphadoxine-Pyrimethamine -
• patients
  weighing gt50kg. 3 tablets stat,
• patients
  weighing lt50kg. 2 tablets stat,
• 
  (provided patient has no sulpha allergy)
• quinine
  600mg TDS for 2 days.
• 2.Quinine 600mg TDS or Quinine sulphate 10mg/kg/8
  hrly for 7 days Doxycycline 100mg BD or
  Tetracycline 500 mg BD for 7 days.
• 3.Mefloquine 750 mg stat, followed by 750 mg
  after 6 hrs. (Pts. Weighing gt 50 kg) or 500mg
  stat followed by 500mg after 6hrs. (Pts.
  Weighing lt 50 kg.)

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Treatment of Resistant Malaria (Complicated
Resistant)

• Ideally all patients with complicated should be
  hospitalized.
• Inj. Quinine IV slowly in Dextrose.
• Higher loading dose is preferred relative to
  maintenance dose.
• In patients requiring more than 48 hours
  parenteral therapy, reduce the maintenance dose
  by ½ rd.
• In presence of renal failure quinine dose should
  be halved after 48 hours.
• Inj. Artemether 160mg IM, then 80mg daily for 4
  days

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Artemether Dosage regimen
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Comparative Efficacy In
Cerebral Malaria
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Arteether Dosage Regimen
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Bulaquine A New generation Anti-malarial drug
Bulaquine a derivative of primaquine developed
by the Central Drug research
Institute in collaboration with W.H.O.,
Advantage - Bulaquine has a biological
activity against the
tissue schizont forms of
Plasmodium Vivax having -
a. A better therapeutic window. b.
Lesser side effects, c. A better
therapeutic index as compared to
current treatment available.

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Mechanism of action of Bulaquine

• In contrast to current Drugs, 8-Aminoquinolones
  are the only drug which act on the liver stage
  and prevent infection by killing liver stages of
  the parasite before merozoites reach blood
  Stream. Thus prevents emergence of either primary
  or secondary attacks.
• Bulaquine Inhibits protein synthesis in protozoa
  and indirectly inhibits Polymerisation of Amino
  acids by the Plasmodia.
• It has also high gametocidal action.

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Dosage of Bulaquine - 25 mg once
daily for 5 days. Should be given with
chloroquine for complete cure
of Vivax malaria.

• INDICATION For the treatment of Vivax malaria
• Contra-indications
• 1. Rheumatoid Arthritis.
• 2. Systematic Lupus erythematosus.
• Concurrent use of Drugs known to cause Haemolysis

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Future of Malarial Treatment

• I. Gene Therapy.
• II. Malarial Vaccine.
• III. Genetic Mapping Plasmodium falciparum.
  
• IV. Low Interleukin-12
  Activity in severe
• Plasmodium falciparum malaria.

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