Malaria • Agent

– Plasmodium falciparum– P. vivax– P. ovale – P. malariae

• Transmission-by the bite of female anopheles mosquitoes

• Occurs throughout the tropics and subtropics at altitudes below 1500 meters

Distributions of malaria

Distribution of falciparum

Drug resistant Malaria

Red - chloroquine resistantGreen - chloroquine sensitiveBlack - chloroquine and mefloquine resistant

3 million deaths/yr. 1 million in Africa,mostly children below the age of 5

Pathology • Hemolysis of infected red cells and adherence of infected

cell to capillary wall• Hemolytic anaemia

• dyserythropoiesis, • splenomegaly • depletion of folate stores

• P. vivax and P. ovale invade reticulocytes• P. malariae normoblastsmost • P. falciparum

• invades red cells of all ages but especially young cells• red cells containing schizonts adhere to capillary

endothelium in brain, kidney, liver, lungs and gut • Malaria immune population

• haemoglobin F, C or especially S –falciparum • lack the Duffy blood group – ovale

Pathology

Pathology

Electronmicroscope view of gut of mosquito

Life cycle of malaria parasite• Female anopheles feed on human blood containing

gametocytes (Sexual form)• Complete sexual cycle in mosquito in 7-10 days and become

sporozoites• Sporozoites inoculated by bite of infected mosquito• Sporozoites leave the blood stream and enter into the

hepatocyte within half and hour• Hepatocytes brust after few days and release merozoites• Merozoites enter into RBCs and multiplication to complete

the asexual life cycle• Merozoites develop into schizont in RBC and release more

merozoites in the blood and peak fever coincide to this time• Ovale and vivex may persist in liver cells as dermant forms

called hypnozoites and capable of producing merozoites months or years later

Incubation period and fever

P. vivax/ P. ovale 8-25 days / TertianP. malariae 15-30 days / QuartanP. falciparum 8-25 days / Aperiodic

Clinical features • P. vivax and P. ovale

• Fever with a rigor• Feeling of cold• Development of high fever • Hot or flush phage• Profuse sweating and gradual fall in fever• Cycle is repeated 48 hours later• Spleen and liver enlarge • Anaemia • Frequent Relapses in the 1st 2 years

Clinical featuresP. malariae

Mild symptoms Bouts of fever every third day. Parasitaemia may persist for many years with

recrudescence of fever, or without producing any symptoms

Causes glomerulonephritis and the nephrotic syndrome in children

P. FALCIPARUM• Most dangerous of the malarias• Onset -insidious, with malaise, headache and

vomiting, and is often mistaken for influenza. • Cough and mild diarrhoea are also common. • The fever has no particular pattern. • Jaundice is common due to haemolysis and

hepatic dysfunction. • The liver and spleen enlarge and become

tender. • Anaemia develops rapidly. • Develop dangerous complications

P Falciparum

Complications of falciparum malariaUnarousable coma/ convulsion /cerebral

malaria Acidemia/acidosis -Arterial pH <7.25 or

plasma bicarbonate level of <15 mmol/LSevere normochromic, normocytic anemia

 Renal failure -Urine output (24 h) of <400

mL in adults or <12 mL/kg in children

Complications of falciparum malariaPulmonary edemaNoncardiogenic pulmonary edema/adult

respiratory distress syndrome Hypoglycemia  Hypotension/shock Bleeding/disseminated intravascular

coagulation Hemoglobinuria / Macroscopic black, brown,

or red urine 

Cerebral malaria• Severe form of malaria• Coma is a characteristic and ominous feature • Despite treatment, is associated with death

rates of ~20% among adults and 15% among children.

• Diffuse symmetric manifestation of encephalopathy

• Focal neurology unusal

Cerebral malaria• No signs of meningeal irritation but resistant to

passive neck flexion • Tonic clonic convulsions• Deep coma• Patient recovering may develop sequale( <3% in

adult and about 15% in child)• Hemiplesia• Cerebral palsy• Cortical blindness• Deafness• Cognitive and learning defect

Features indicating poor prognosis in falciparum malariaClinical Parameter

Marked agitation Hyperventilation (respiratory distress) Hypothermia (<36.5°C) BleedingDeep coma Repeated convulsions Anuria Shock

Laboratory parameterBiochemistry

Hypoglycemia (<2.2 mmol/L) Hyperlactatemia (>5 mmol/L) Acidosis (arterial pH <7.3, HCO3 <15 mmol/L) Elevated serum creatinine (>265 mol/L) Elevated total bilirubin (>50 mol/L) Elevated liver enzymes (AST/ALT X 3 times ) Elevated muscle enzymes (CPK , myoglobin ) Elevated urate (>600 mol/L)

Laboratory parameter Hematology

Leukocytosis (>12,000/L)Severe anemia (PCV <15%) Coagulopathy Decreased platelet count (<50,000/L) Prolonged prothrombin time (>3 s) Prolonged partial thromboplastin time Decreased fibrinogen (<200 mg/dL)

Diagnosis of Malaria

Diagnosis • Thick blood film

• Low parasitemia- thick film erythrocytes are lysed, releasing all blood stages of the parasite

• Thin film • confirm the diagnosis, • to identify the species of parasite • P. falciparum, only ring forms

• Immunochromatographic 'dipstick' tests or plasmodium LDH test

Management • P. vivax, P. ovale and P. malariae

• Chloroquine: 600 mg chloroquine base followed by 300 mg base in 6 hours, then 150 mg base 12-hourly for 2 more days

• Mild falciparum malaria• Quinine dihydrochloride or sulphate drug of

choice -600 mg salt (10 mg/kg) 8-hourly by mouth is given until the patient is clinically better ,followed by a single dose of sulfadoxine 1.5 g combined with pyrimethamine 75 mg, i.e. 3 tablets of Fansidar

Management of mild falciparum• Sulphonamide sensitivity

• quinine may be followed by doxycycline 100 mg daily for 7 days

• Atovaquone 250 mg plus proguanil 100 mg (Malarone)

• 4 tablets once daily for 3 days• Artemether plus Mefloquine• Artemether 200 mg/day orally for 5 days then mefloquine

500 mg in 2 doses 2 hours apart• Pregnancy a 7-day course of quinine alone

Management of severe malaria• Early and appropriate antimalarial drugs • Active treatment of complications • Correction of fluid, electrolyte • Acid-base balance• Avoid hypoglycemia• Avoidance of harmful ancillary treatments

Radical cure of malaria • P. vivax and P. ovale

• Primaquine (15 mg daily for 14 days)• Destroys the hypnozoite phase in the liver • S/E-• Haemolysis (G6PD)-deficient• Cyanosis due to the formation of methaemoglobin

Chemoprophylaxis of malaria• Chloroquine resistance high

• Mefloquine 250 mg once weekly • Doxycycline 100 mg daily• Malarone 100 mg daily• 1 tablet from 1-2 days before travelling to 1 week

after return • Chloroquine resistance moderate

• Chloroquine plus Proguanil 150 mg base+100 mg (Two tablets weekly+Two tablets daily )

• Chloroquine resistance absent • Chloroquine or Proguanil 150 mg base or 100 mg

(Two tablets weekly/One or two tablets daily)

Malaria control in endemic areas• Sanitation and improvement in living

condition• Avoid mosquito bites• Permethrin-impregnated bed nets • DDT and insecticide spray• Malaria vaccine under evaluation, in Thailand

and Africa

Prevention

Prevention

Personal protection against malaria• Avoidance of exposure to mosquitoes at their

peak feeding times (usually dusk and dawn) and throughout the night

• Insect repellents creams • Suitable clothing – full sleeve• Widespread use of insecticide-impregnated

bed nets or other materials