This lecture was conducted during the Nephrology Unit Grand Ground by Medical Students rotated under

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This lecture was conducted during the Nephrology
Unit Grand Ground by Medical Students rotated
under Nephrology Division under the supervision
and administration of Prof. Jamal Al Wakeel, Head
of Nephrology Unit, Department of Medicine and
Dr. Abdulkareem Al Suwaida, Chairman of
Department of Medicine. Nephrology Division is
not responsible for the content of the
presentation for it is intended for learning and
/or education purpose only.
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Malaria

• Presented by
• Bader Alajlan, Rayan Alalola, Faisal Obeid
• Medical Students
• July 2008

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malaria

• Introduction
• Classification
• Epidemiology
• Pathogenesis
• Symptoms and signs
• Diagnosis
• Treatment and prevention
• Complication

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Introduction

• Malaria is a tropic life threatening disease.
• Humans are infected with Plasmodium protozoa when
  bitten by an infective female Anopheles mosquito
  vector.
• Symptoms may appear within weeks to months or
  even years.

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Classification

• There are 4 species
• plasmodium falciparum
• plasmodium vivax
• plasmodium ovale
• plasmodium malariae

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Diagnosis

• Timely diagnosis of the correct species is
  required because the particular species of P
  falciparum can be fatal and is often resistant to
  standard chloroquine treatment.
• Species can usually be distinguished by
  morphology on a blood smear.

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Epidemiology
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Pathogenesis
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Symptoms and signs

• Depends on the type of malaria
• P. falciparum
• The most dangerous type.
• Insidious onset.
• Malaise, headache, vomiting.
• Fever.
• Cough, diarrhea.
• Jaundice.
• Tender hepatosplenomegaly.
• Anemia develops rapidly.

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Symptomology

• P.vivax and P.oval
• Fever classically every 48 h.
• Rigors.
• Gradual hepatosplenomegaly.
• Anemia develops slowly.
• Relapse is common.

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Symptomology

• P.malariea
• Fever every third day.
• Mild symptoms.
• Parasitaemia may persist for many years.
• Causes glomerulonephritis and nephrotic syndrome
  in children.

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Diagnosis

• Malaria should be suspected clinically!!
• Thick and thin blood films
• Thick film are 20 times more sensitive than thin
  smears, but speciation may be more difficult.
• Thin films essential to confirm the diagnosis
  and to identify the species of the parasite.
• and In P.falciparum to quantify the parasite
  load.

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Blood films

• P.falciparum

• P.malariea

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Diagnosis

• P.vivax

• P.ovale

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Diagnosis

• Immunochromatographic dipstick test for
  P.falciparum
• should be used parallel with blood film
  examination.

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Laboratory Investigations

• Others
• CBC low Hb, low platelets
• Blood cultures
• Hypoglycemia to rule out cerebral malaria
• Urea and creatinine.

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Treatment (based on WHO recommendations 2006)

• Rx of uncomplicated P.falciparum
• Rx of sever malaria
• Rx of P.vivax, P.ovale, P.malariae
• Prevention

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Definitions

• Uncomplicated malaria symptomatic malaria
  without signs of vital organ dysfunction.

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Definitions

• Complicated malaria
• Clinical features
• Prostration.
• Impaired consciousness.
• Respiratory distress.
• Convulsions.
• Circulatory collapse.
• Pulmonary edema.
• Jaundice.
• Abnormal bleeding.

• Laboratory test
• Sever anemia.
• Hypoglycemia.
• Acidosis.
• Renal impairment.
• Hyperlactemia.
• Hyperparasitemia.

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Treatment

• Combination therapy is the use of 2 or more
  blood schizontocidal drugs with different modes
  of action.

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Rx of uncomplicated P.falciparum

• Artemisinis combination are the best.
• MOA
• production of free radicals that kill the
  parasite.
• Active against all human malaria parasites.
• Does not affect the hepatic stage.
• Artesunate 100 mg amodiaquine 270 mg BID for 3
  days.
• Artemether lumefantrine (Riamet) 4 tabs/12h
  for 6 doses.

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Treatment

• These combinations are better than the quinine
  regimens quinine doxycycline
• Which are now considered as second line.

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Rx of sever malaria

• Atresunate 2.4 mg/kg IV or IM given on admission
  then after 12h and 24h, then once daily.
• Fluid therapy for rehydration.
• Blood transfusion usually used in children,
  because anemia is sever (Hb lt 5 g/dl)

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Rx of sever malaria

• Exchange blood transfusion
• No solid evidence that showed reduce in
  mortality.
• It could be used to reduce the parasite burden.
• ?? Steroids one study showed no significant
  difference in mortality.
• Their recommendation dont use steroids.

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Rx of P.vivax, P.ovale, P.malariae

• Chloroquine
• For radical cure of P.vivax and P.ovale
• Primaquine 15 mg daily for 14 days.
• It destroys the hypnozoite phase in the liver.
• It may cause hemolysis with G6PD deficient
  patients.

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Prevention

• Avoid mosquito bites
• Wearing long sleeves, trousers.
• Nets.
• Repellent creams or sprays.

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Prevention

• Chemoprophylaxis
• Should be given 1 week before traveling, and
  continued 4 weeks after leaving.

• Depends on the area of travel (ie. Chloroquine
  resistance or not)

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Complication of malaria
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• Malaria is probably the only infection that can
  be treated in just three days, yet that kills
  millions every year .
• Malaria may become a medical emergency by
  rapidly progressing to complications and death.
• Early diagnosis proper management can prevent
  serious complication.
• Most complications have similar pathogenesis .

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Predisposing factors for complications

• (1.) Extremes of age.
• (2.) Pregnancy, especially in primigravidae and
  in 2nd half of pregnancy.
• (3.) Immunosuppressed - patients on steroids,
  anti- cancer drugs, immunosuppressant drugs.
• (4.) Immunocompromised - patients with advanced
  tuberculosis and cancers.
• (5.) Splenectomy.
• (6.) Lack of previous exposure to malaria
  (non-immune) or lapsed immunity
• (7.) Pre-existing organ failure.

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• Complications of P. falciparum malaria
• Cerebral malaria ( coma )
• Convulsions
• Hyperpyrexia
• Severe anemia
• Metabolic (Lactic) Acidosis
• jaundice
• renal failure
• Pulmonary odema ARDS
• hypoglycemia
• Hypotention shock
• Bleeding clotting disorder
• haemoglobinuria
• hyperparasitemia
• Associated infection

• Complications of P. vivax / P. malariae
• Rupture of spleen
• Hepatic dysfunction
• Thrombocytopenia
• Severe anemia
• malarial nephropathy

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Cerebral Malaria

• In falciparum malaria, 10 of all admissions and
  80 of deaths are due to the C.N.S. involvement
• Manifestations of cerebral dysfunction include
  any degree of impaired consciousness, delirium,
  abnormal neurological signs, and focal and
  generalized convulsions
• For a diagnosis of cerebral malaria, the
  following criteria should be met(i.) Deep,
  unarousable coma Motor response to noxious
  stimuli is non-localising or absent.(ii.)
  Exclusion of other encephalopathies.(iii.)
  Confirmation of P. falciparum infection
• all patients with P. falciparum malaria with
  neurological manifestations of any degree should
  be treated as cases of cerebral malaria.

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• its pathophysiology is not completely understood
• underlying defect seems to be clogging of the
  cerebral micocirculation by the parasitized red
  cells.
• Obstruction to the cerebral microcirculation
  results in hypoxia and increased lactate
  production due to anaerobic glycolysis
• In patients with cerebral malaria, C.S.F. lactate
  levels are high and significantly higher in fatal
  cases
• complete obstruction to blood flow is unlikely,
  since the survivors rarely have any permanent
  neurological deficit.
• Causes of neurological manifestations in malaria
  
• High-grade fever
• Antimalarial drugs
• Hypoglycemia
• Hyponatremia
• Severe anaemia

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Management of cerebral malaria

• Manage airway
• Nurse by side
• Phenobarbitone IM, 10-15 mg/kg body weight should
  be given y to prevent convulsions
• Antimalarial treatment Parenteral Quinine has
  been traditionally the treatment of choice for
  cerebral malaria
• 20mg of salt/kg diluted in 10 ml/kg isotonic
  fluid, infused over 4 hrs then 10 mg of salt /
  kg over 4 hrs, every 8-12 hrs until patient can
  swallow.
• Do not administer the following Corticosteroids
  other anti inflammatory drugs anti oedema drugs
  like mannitol, urea, invert sugar low molecular
  weight dextran adrenaline heparin
  pentoxifylline hyperbaric oxygen ciclosporin
  etc

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Metabolic (Lactic) Acidosis

• Increased production of lactic acid by parasites
• Decreased clearance by the liver
• Most importantly the combined effects of several
  factors that reduce oxygen delivery to tissues
• Marked reductions in the deformability of
  uninfected RBCs  may compromise blood flow
  through tissues
• Dehydrated and hypovolemia can exacerbates
  microvascular obstruction by reducing perfusion
  pressure
• Destruction of RBCs and anemia further
  compromises oxygen delivery

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Acute Pulmonary Odema

• It is a fatal complication of severe falciparum
  malaria with more than 50 mortality .
• In a few patients it could be due to fluid
  overload
• increased permeability of pulmonary capillaries.
  Sequestration of red cells and clogging of
  pulmonary microcirculation and disseminated
  intravascular coagulation
• more common in patients with hyperparasitemia,
  renal failure and pregnancy .
• Shock
• Hypotension in malaria could be due to many
  reasons
• Dehydration due to high-grade fever, excessive
  sweating and inadequate fluid intake.
• Dehydration due to vomiting and/or diarrhoea.
• Pulmonary oedema.
• Metabolic acidosis.
• Associated Gram negative septicemia.
• Massive gastrointestinal haemorrhage

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Renal Failure

• Renal dysfunction in falciparum malaria can be
  due to many factors
• Renal failure in malaria is caused by renal
  cortical vasoconstriction and resultant
  hypoperfusion, sequestration and resultant acute
  tubular necrosis due to microvascular obstruction
  and due to massive intravascular hemolysis in
  blackwater fever .
• Quartan malarial nephropathy
• In areas where P. malariae is prevalent
• immune-complex mediated glomerulonephritis,
  leading to nephrotic syndrome
• Histologically there is progressive focal and
  segmental glomerulosclerosis with fibrillary
  splitting or flaking of the capillary basement
  membrane.
• Patients usually present by the age of 15 years
  with typical features of nephrotic syndrome.
• Treatment with antimalarial drugs,
  corticosteroids or cytotoxic agents may not be
  useful.

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Anemia

• In falciparum malaria, anemia can develop rapidly
  due to profound hemolysis
• The degree of anemia correlates with parasitemia
  and schizontemia
• More serious in children and pregnant .
• Bleeding disorder
• Thrombocytopenia
• Disseminated intravascular coagulation

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Hypoglycemia

• Hypoglycemia in malaria may be asymptomatic
• Therefore, hypoglycemia, which is easily
  treatable, may be missed
• Causes
• 1. Increased consumption of glucose by the host
  and the growing parasites.
• 2. Failure of hepatic gluconeogenesis and
  glycogenolysis as a result of impaired liver
  function and acidemia and hyperinsulinemia
• 3. Stimulation of pancreatic insulin secretion by
  drugs like quinine. More than one of these
  factors may be at play in a given patient
• Jaundice
• Malaria is the most common cause for jaundice in
  a malarious area
• Most often it is caused by hemolysis , rarely due
  to liver impairment .
• Hepatic dysfunction more with vivax malaria ,
• Fever, jaundice, tender hepatomegaly, mild
  elevation in the levels of hepatic enzymes and
  bilirubin are observed
• Liver function returns to normal shortly after
  antimalarial treatment

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Rupture of spleen

• It is more common in vivax malaria than
  falciparum malaria
• occur in up to 0.7 of the patients
• Rupture occurs in acute, rapid, hyperplastic
  enlargement of spleen
• Patients present with abdominal pain, fever,
  tachycardia, prostration and rapidly developing
  anemia and hypotension.
• Ultra sound evaluation of abdomen and
  paracentesis of the abdomen can confirm the
  diagnosis
• Treatment includes replacement of fluid and
  blood, laparotomy and splenectomy

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Complication due to medication

• Vomiting
• Dizziness
• Itching ( chloroquine )
• Abdominal pain
• Convulsion ( chloroquine , quinine, meflequine )
• Coma ( chloroquine , quinine)
• Hypoglycemia ( quinine)
• Anemia , jaudice ,Haemoglobinuria ( primaquine in
  pt with G6PD deficiency )
• fever

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References

• emedicine.com/med/TOPIC1385.HTM
• Guidelines for the treatment of malaria 2006
  (WHO)
• Principles and practice of medicine, Davidsons
  (19th edition)
• Oxford handbook of clinical medicine (7th
  edition)
• www.malariasite.com

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thanks