malaria

 Introduction
 Classification
 Epidemiology
 Pathogenesis
 Symptoms and signs
 Diagnosis
 Treatment and prevention
 Complication
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.
Classification

 There are 4 species:

 plasmodium falciparum
 plasmodium vivax
 plasmodium ovale
 plasmodium malariae
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.
Epidemiology
Pathogenesis
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.
Symptomology
 P.vivax and P.oval:
 Fever: classically every 48 h.
 Rigors.
 Gradual hepatosplenomegaly.
 Anemia develops slowly.
 Relapse is common.
Symptomology
P.malariea:
 Fever: every third day.
 Mild symptoms.
 Parasitaemia may persist for many years.
 Causes glomerulonephritis and nephrotic syndrome
in children.
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.
Blood films
 P.falciparum  P.malariea
Diagnosis
 P.vivax  P.ovale
Diagnosis

 Immunochromatographic “dipstick” test for

P.falciparum
 should be used parallel with blood film
examination.
Laboratory Investigations

 Others:
 CBC: low Hb, low platelets
 Blood cultures
 Hypoglycemia – to rule out cerebral malaria
 Urea and creatinine.
Treatment (based on WHO
recommendations 2006)
 Rx of uncomplicated P.falciparum
 Rx of sever malaria
 Rx of P.vivax, P.ovale, P.malariae
 Prevention
Definitions

 Uncomplicated malaria: symptomatic

malaria without signs of vital organ
dysfunction.
Definitions
 Complicated
malaria:
 Clinical features:  Laboratory test:
 Prostration.  Sever anemia.
 Impaired  Hypoglycemia.
consciousness.  Acidosis.
 Respiratory distress.  Renal impairment.
 Convulsions.  Hyperlactemia.
 Circulatory collapse.  Hyperparasitemia.
 Pulmonary edema.
 Jaundice.
 Abnormal bleeding.
 Treatment

 Combination therapy: is the use of 2 or

more blood schizontocidal drugs with
different modes of action.
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.
Treatment

 These combinations are better than the

quinine regimens: quinine + doxycycline

 Which are now considered as second line.

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 < 5 g/dl)
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: don’t use steroids.
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.
Prevention

 Avoid mosquito bites:

Wearing long sleeves, trousers.
Nets.
Repellent creams or sprays.
Prevention
 Chemoprophylaxis:
 Should be given 1 week  Depends on the area of
before traveling, and travel (ie. Chloroquine
continued 4 weeks after resistance or not)
leaving.
Area Antimalarial
Chloroquine resistance Mefloquine
high (or doxycycline or
malarone)
Chloroquine resistance Chloroquine +
moderate proguanil
Chloroquine sensitive Chloroqunie
Or proguanil
Complication of malaria
 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 .
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.
 Complications of P.  Complications of P. vivax /
falciparum malaria P. malariae

 Cerebral malaria ( coma )  Rupture of spleen

 Convulsions  Hepatic dysfunction
 Hyperpyrexia  Thrombocytopenia
 Severe anemia  Severe anemia
 Metabolic (Lactic) Acidosis  malarial nephropathy
 jaundice
 renal failure
 Pulmonary odema & ARDS
 hypoglycemia
 Hypotention & shock
 Bleeding & clotting disorder
 haemoglobinuria
 hyperparasitemia
 Associated infection
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.
 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
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
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
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
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.
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
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
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
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
References

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