PARASITOLOGY LECTURE 13 – Malaria – Dr. Carandang Notes from Lecture
USTMED ’07 Sec C – AsM MALARIA
- “Malaria” (“Paludisme”) - Mal – bad
- Aria – air - Palus (marsh)
-
disease was caused by vaports and mists arising from swampHISTORY
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5th Century B.C.o
Hippocrates – first to describe the clinical picture of malaria and some complications of the disease- 1880
o
Laveran – first described the malarial parasites in blood films of man (asexual stage of P. falciparum)Geographic distribution of malaria in the mid-19th century (malarious areas are shaded)
- 1955
o W.H.O. adapted the concept of malarial eradication
Worldwide range of malaria in 1994 (darker shading)
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Malaria free areas (no vector transmission) o Manila proper o Aklan o Capiz o Guimara o Siquijor o Biliran o Iloilo o Leyte Norte o Leyte Sur o Northern Samar o Camiguin o Cebu o Leyte o Catanduanes - Philippine Statistics o DOH 2001
40,543 cases / yr Morbidity rate of 52/100,000 population ETIOLOGY• In the Philippines, in order of frequency
o Plasmodium falciparum (most frequent) o Plasmodium vivax
o Mixed infection (Pf and Pv) o Plasmodium malariae
o Plasmodium ovale (exclusively rare)
HUMAN MALARIAL PARASITES
PARASITES DISEASE
Plasmodium vivax Benign tertian malaria Plasmodium ovale Benign tertian malaria Plasmodium falciparum Malignant tertian malaria
Plasmodium malariae Quartan malaria
MODE OF TRANSMISSION
• Through the bite of female anopheles mosquito
• Directly from one person to another by passage of blood containing erythrocytic parasite through:
o Blood transfusion
o Sharing of contaminated syringes and needles o Mingling of infected maternal blood with that
of infant during birth process (neonatal malaria)
o Transplacental transmission (congenital malaria)
VECTORS OF MALARIA IN THE PHILIPPINES
• Principal vector – Anopheles flavirostris minimus • Secondary vector o Anopheles litoralis o Anopheles balabacensis o Anopheles mangyanus
o
Anopheles maculates LIFE CYCLEMosquito Cycle (Sporogany)
PATHOPHYSIOLOGY
• Degree of damage to tissue depends on o Species
o Parasite concentration
TISSUE ANOXIA
• Basic pathophysiology changes in malaria
4 MECHANISMS LEADING TO TISSUE ANOXIA • Anemia – hemolysis • Changes in blood flow
• Changes in capillary endothelium • Histotoxic anoxia
1. Anemia-hemolysis
- Intravascular – rupture of infected and non-infected rbc - Extravascular – phagocytosis of infected and
non-infected rbc by R.E. cells (Kupffer cells in the liver, macrophages in spleen, lungs and bone marrow)
- Bone marrow dysfunction (dyserythropoeisis) – persist for days or weeks following acute malaria
Characteristics of parasitized red cells • Decreased deformability • Increased adhesion • Increased fragility
• Decreased oxygen transport • Antigen release
• Toxin production 2. Changes in blood flow - Blockage of small blood vessels
- Vasomotor changes – vasoconstriction of arterioles and venules, vasodilation of capillaries
Blockage of small vessels is brought about by:
• Cytoadherence – mature forms of parasite (P. falciparum) first roll on and then adhere to the microvascular epithelium
•
Reduction in deformability of the parasitized erythrocytes due to:o Reduced membrane fluidity o Increasing sphericity
o
Enlarging and relatively viscous intraerythrocytic parasiteErythrocyte adhesion (rosetting) of infected rbc with two or more uninfected rbc
Rosetting of P. falciparum in vitro
Consequences of Microcirculatory Obstruction
• Reduced oxygen and substrate supply leading to anaerobic glycolysis and lactic acidosis
3. Changes in capillary endothelium
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Increased permeability cerebral edema, hypovolemic shock4. Histotoxic anoxia
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Respiration (oxidative phosphorytation of the mitochondria) is inhibitedPARASITE VIRULENCE FACTORS • Multiplication Capacity
- A rapidly expanding biomass of parasites is more likely to outstrip host defenses
- Immunity reduces multiplication and then limits the size of the parasite biomass
• Red cell selectivity
- Unselective parasite will not be limited by the availability of suitable red cells
o P. vivax prefers young rbc o P. malariae prefers old rbc
o P. falciparum infectes all stages of rbc • Cytoadherence and rosetting ability
o Parasites with both these adhesive characteristics may be more pathogenic o All four Plasmodium species normally infecting
man can induce rosetting but only P. falciparum causes lethal infection
o Only P. falciparum causes cytoadherence and all parasites sequester in vivo
• Potential to induce cytokine release
o Cytokines are responsible for many of the symptoms and signs of malaria, particularly fever and malaise
• Anitigenicity
o Parasites that are not recognized by the host will obviously have a relative growth advantage
• Antimalarial drug resistance
o In many areas of the tropics, antimalarial drugs are widely available and self-medication is common
“Toxins” liberated when mature schizont ruptures: • Cytokines (TNF)
• Phospholipid material
- Both have endotoxin like activity
- Causes symptoms and signs of the paroxysm such as shivering, cool extremities, headache, chills, fever, malaise, followed by sweating, vasodilation, and defervesence
• Nitric oxide(No) may cause many of the pathological features of severe malaria which include hypotension, lactic acidosis, hypoglycemia and coma
Other effects of cytokine: • Placental dysfunction • Suppression of erythropoiesis • Hepatic dysfunction • Inhibition of gluconeogenesis
• Promote cytoadherence by up regulating the endothelial expression of some vascular ligands for P. falciparum infected rbc particularly ICAM-I, the principal receptor of cerebral vascular epithelium
• Mediators of parasite killing by activating leucocytes and other cells to release nitric oxide generating parasitidal lipid peroxides
BLACKWATER FEVER (G6PD)
• Refers to massive intravascular hemolysis and the passage of dark red, brown, or usually black urine • More common in G6Pd deficient patients receiving sulfa
containing drugs, quinine, or artemisinin
• Occurs in severe falciparum malaria in patients without G6PD deficiency but was given quinine or artermisinin
LIVER DYSFUNCTION
• Jaundice is common
• Decreased in clotting factor synthesis • Decreased metabolic clearance of drugs • Decreased biliary excretion
•
Failure of gluconeogenesis lactic acidosis and hypoglycemiaHYPOGLYCEMIA
• Associated closely with hyperlactatemia
• In adults, increased glucose demand predominates while in children, reduced glucose supply may be more important
• Stimulation of pancreatic B cell insulin secretion in quinine treated patients (occurs after the first 24 hours of treatment)
ACIDOSIS
• Mainly caused by lactic acid due to o Tissue anaerobic glycolysis o Reduced circulating red cell o Reduced oxygen carriage
o Increased glycolysis (as part of hypermetabolic state)
o Decreased hepatic and renal lactate clearance o Lactate production by malaria parasites
GASTROINTESTINAL DYSFUNCTION
• Minor stress ulceration of the stomach and duodenum • Pattern of malabsorption due to reduced splanchnic
perfusion (secondary to gut sequestration and visceral vasoconstriction)
PLACENTAL DYSFUNCTION
• Pregnancy increases susceptibility to malaria due to suppression of systemic and placental cell-mediated immune response
•
There is intense sequestration of falciparum infected rbc in the placenta leading to thickened syncitiotrophoblast, abnormal uteroplacental blood flow, and placental insufficiency fetal growth retardationPULMONARY EDEMA
•
Results from sudden increase in pulmonary capillary permeabiltiy that is not reflected in other vascular body • Cause of this increase in permeability is not knownRENAL FAILURE
• Common manifestation of falciparum malaria in adults • Basic pathology is acute tubular necrosis (mechanism
remain unclear)
•
Sequestration is greatest in the medullary vessels and it is in the medulla where tissue PO2 is lowest and mostvulnerable to ischemia and further hypoxia
COAGULOPATHY AND THROMBOCYTOPENIA
• There is acclerated coagulation cascade activity o Accelerated fibrinogen turnover
o Consumption of antithrombin III, protein C, and protein S
o Increased concentrations of plasminogen activator inhibitor-I and fibrin degradation products
o Thrombocytopenia due to increased splenic clearance (moderate in P. vivax and falciparum, severe in falciparum)
Reasons for bacteria superinfection in severe malaria • Broader immune suppression due to:
o Defects in monocytes and neutrophil chemotaxis
o Reduced monocytic phagocytic function
COMA IN CEREBRAL MALARIA
• Associated with 15-20% mortality
• 90% of children and 98% of adults survivors recover without sequelae
• Involve neurotransmitter abnormalities and nitric oxide, which is a potent inhibitor of neurotransmission
DIAGNOSIS
• Clinical manifestation
• History of coming from an endemic area or recent blood transfusion
• Demonstration of asexual forms of plasmodia in thin and thick peripheral blood smears; if negative, repeat as often as necessary depending on the severity of the manifestations; at times, in the bone marrow
PLASMODIUM FALCIPARUM
PLASMODIUM VIVAX
PLASMODIUM OVALE
DIAGNOSIS
• Quantitative Buffy Coat (QBC)
• Para sight F test – a dipstick test for the simple and rapid diagnosis of P. falciparum
• Serologic test (IFA) – cannot distinguish between current and past infection, therefore not helpful in establishing the diagnosis of an acute infection.
RATIONALE AND TECHNIQUE OF MALARIA CONTROL
The right way (above) and the wrong way(below) of using the bed net.
Outdoor control of mosquitoes by sapce spraying in a rural area of Singapore, using Dieldrin and a portable “Swingfog” fogging machine.
Larvivorous fish (Gambusia affinis) widely used for mosquito control in many parts of the world
Larvivorous fish used in some malaria control programmes. These are two species of “annual fish” of the family Cyprinodontidae.
Differentiation of Anopheles, Aedes and Culex mosquitoes at various stages of their development
