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 swamp HISTORY - 5 th 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) - 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 CYCLE Mosquito Cycle (Sporogany) Human Cycle Schizogony
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PARASITOLOGY LECTURE 13 – Malaria – Dr. CarandangNotes from LectureUSTMED ’07 Sec C – AsM
MALARIA
- “Malaria” (“Paludisme”)- Mal – bad- Aria – air- Palus (marsh)- disease was caused by vaports and mists arising
from swamp
HISTORY
- 5th Century B.C.o Hippocrates – first to describe the clinical
picture of malaria and some complications of the disease
- 1880o 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)
- 1955o W.H.O. adapted the concept of malarial
eradication
Worldwide range of malaria in 1994 (darker shading)
In the Philippines, in order of frequencyo Plasmodium falciparum (most frequent)o Plasmodium vivaxo Mixed infection (Pf and Pv)o Plasmodium malariaeo Plasmodium ovale (exclusively rare)
Through the bite of female anopheles mosquito Directly from one person to another by passage of
blood containing erythrocytic parasite through:o Blood transfusiono Sharing of contaminated syringes and
needleso 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 litoraliso Anopheles balabacensiso Anopheles mangyanuso Anopheles maculates
LIFE CYCLE
Mosquito Cycle (Sporogany)
Human Cycle Schizogony
PATHOPHYSIOLOGY
Degree of damage to tissue depends ono Specieso 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 fluidityo Increasing sphericityo Enlarging and relatively viscous
intraerythrocytic parasite
Erythrocyte 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- Increased permeability cerebral edema,
hypovolemic shock 4. Histotoxic anoxia- Respiration (oxidative phosphorytation of the
mitochondria) is inhibited
PARASITE 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 cellso P. vivax prefers young rbco P. malariae prefers old rbco P. falciparum infectes all stages of rbc
Cytoadherence and rosetting abilityo Parasites with both these adhesive
characteristics may be more pathogenico 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 releaseo Cytokines are responsible for many of the
symptoms and signs of malaria, particularly fever and malaise
Anitigenicityo 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
hypoglycemia
HYPOGLYCEMIA
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 too Tissue anaerobic glycolysiso Reduced circulating red cell o Reduced oxygen carriageo Increased glycolysis (as part of
hypermetabolic state)o Decreased hepatic and renal lactate
clearanceo 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 retardation
PULMONARY 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 known
RENAL 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 most vulnerable to ischemia and further hypoxia
COAGULOPATHY AND THROMBOCYTOPENIA
There is acclerated coagulation cascade activityo Accelerated fibrinogen turnovero Consumption of antithrombin III, protein
C, and protein So 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
PLASMODIUM MALARIAE
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