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3. Increased phagocytic activity in the liver and
PATHOPHYSIOLOGY spleen à hyperplasia of Kupffer cells, monocytes/
macrophages à hepatosplenomegaly
1. Parasitized RBC’s (Red cells that have been attacked by 4. Increased red cell destruction à anemia,
merozoites) will: hypotension, jaundice, hemosiderin deposition
5. P. falciparum stimulates production of cytokines
a. Adhere to each other (“cytoadherence” or
“rosetting”) & to (visceral) capillary endothelium P. falciparum Causes a More Severe Disease Because of the
(“intravascular sequestration”) producing fibrin thrombi à ff:
Ischemia/ microinfarcts due to formed microthrombi • It can infect RBCs of any age
• Causes infected RBCs to clump together and stick to
Brain – encephalopathy the endothelium
o PfEMP1 – facilitates sticking/rosetting/
Heart – CHF
cytoadherence to the endothelium
Lungs – pulmonary edema o When they stick to the endothelium, they
are sequestered in the small vessels
Other organs
resulting in decreased tissue perfusion
Lecture: This is especially true for P. falciparum. Intravascular • It causes GPI-linked proteins are released from the
sequestration mostly occurs in the deeper vital organs hence we infected red cells
only see the younger forms in the peripheral blood.
o Induces cytokine production by the host
cells (TNF, IFNy, IL-1)
b. adhere to normal red cells forming rosettes o Cytokines:
(aggregates) à easily sequestered or trapped in organs § Suppress RBC production
§ Induce fever
c. Be phagocytosed (with normal red cells) by fixed § Stimulate production of reactive
macrophages in the spleen & liver à increased red cell nitrogen species à tissue damage
destruction § Induce expression of PfEMP1
d. Be rigid with less deformability Plasmodium falciparum
• Sequestration of growing parasites in deep tissues
Lecture: Become rigid and less deformable may be due to changes in
phospholipid layer or red cell membrane, etc. à not able to pass where the environment favors their maturation
through the sinusoids à trapped à leads to their destruction • Ring forms are seen in peripheral blood
• They escape by the spleen and hence undergo
2. Ruptured RBC’s release: unbridled multiplication
a. Hemoglobin à hemoglobinuric nephrosis Pathologic Changes in Organs are Due to the Effects of:
*Excretion of Hb in the urine thus it turns
into a dark color • Adherence of red cells to each other and to vascular
endothelium à MICROVASCULAR OBSTRUTION
Lecture: Hemozoin – derived from the heme that results from the o Congestion & reduced blood flow
breakdown of Hb. Heme is considered toxic to the cell so parasites o Tissue hypoxia and microinfarcts
convert heme into a crystalized form (called Hemozoin). This
deposits in the organs such as spleen and liver making them have a • Destruction of both parasitized and normal cells
dark color o Rupture (INTRAVASCULAR HEMOLYSIS) –
breakdown of the red cells occurs within
the blood vessels
b. Malarial pigment (iron and protein; hemozoin) à § Anemia
slate gray or black spleen and liver
§ Jaundice
c. Parasites
§ Hypotension
d. Cells debris
§ Hemozoin deposition
e. Pyrogens à chills and fever
§ Hemoglobinuric nephrosis
§ Release of pyrogens
• Increased phagocytic activity in the liver and spleen MECHANISM OF HOST RESISTANCE
• Lymphoid and reticulo-endothelial hyperplasia -> 1. Inherited alteration in red cells
hepatosplenomegaly • Absence of Duffy Antigen
• Anemia § Merozoite receptors are associaret with Duffy
• Hemosiderin deposition factors on red cells
PHYSIOLOGIC METABOLIC EFFECTS § If you do not have this antigen, you become
1. Blood volume becomes difficult to regulate resistant to malaria
• in the face of fever, moderate § West Africa: 90% lack Duffy factors
hyponatremia and increased capillary § Most blacks are insusceptible to P. vivax
permeability malaria
2. Anemia – due to repeated hemolysis o Sickle Hb Trait
1. Usually normocytic, hypochromic § confers resistance to P. falciparum
2. P. vivax – invades young cells o Parasitized red cells sickle much more
3. P. malariae – invades mature RBCs readily & hence are sequestered
4. P. falciparum – invades both à rapid o Hgb C
development of anemia in falciparum malaria o Resistant to osmotic lysis hence cannot
3. Thrombocytopenia burst & release merozoite
• due to sequestration of platelets in the o Modulates cell surface properties of
spleen infected red cell (decreased
aggregation)
4. Hypoglycemia – due to:
1. Glucose utilization by parasites 2. G6PD Deficiency
2. Inhibition of gluconeogenesis
3. Stimulation of ancreatic insulin secretion by • may limit Parasitemia
drugs like quinine
3. Repeated or Prolonged Exposure
COMPLICATIONS
• Generally, repeated infections are required to
1. Immune Complex Disorders
develop immunity
• Nephrotic syndrome
§ Immunity to one species does not
o Immune complex binds to basement
protect against other species
membrane of glomerular capillaries
§ Infants do not become infected
o Generation of C3a and C5a
during the first 3-4 months
o Accumulation of PMNs and macrophages
o Production of NO, ROS, and release of
LYMPHATIC FILARIASIS
enzymes
o Focal necrosis
o Glomerular sclerosis ETIOLOGIC AGENTS
• Tropical Splenomegaly Syndrome
o Hypersplenism • Wuchereria bancrofti
o High malarial Ab titers • Brugia malayi
o Elevated serum IgG & IgM
VECTOR
TROPICAL SPLENOMEGALY SYNDROME • Culex quinquefasciatus
Hyperactive malarial splenomegaly o in the tropics
In endemic areas (equatorial regions of Africa, Asia, • Others: Aedes, Anopheles, Mansonia
Middle East, South America)
Repeated exposures cause an exaggerated production if
IgM
Accompanied by lymphocytic inflitration in liver and
spleen
COMMON TROPICAL INFECTIONS OF THE CVS 4
Dr. Debbi D. de la Fuente
LIFE CYCLE o Subcutaneous fibrosis
o Epithelial hyperkeratosis
SPECTRUM OF DISEASE
• Asymptomatic Microfilaremia
o Microfilaria are present in the blood
without the patient experiencing symptoms
o Associated with filarial specific Th2 helper
cells that down-regulate Th1 helper cells
and
o inhibit granuloma formation
o Moderate enlargement of lymph nodes
o Numerous microfilaria in the blood
o Eventually adult worms die and microfilaria
disappear
o Usually seen in endemic areas where
children are exposed at an early age
Figure 2: Summary of Life Cycle of Filariasis: Mosquito bite → • Acute adenolymphangitis or recurrent
Filariform larva transferred to skin → penetrate skin → Lymphatic lymphadenitis
vessels & sinuses of lymph nodes → mature into adult worms that a. Sudden onset of high-grade fever, painful
mate → give rise to microfilaria → microfilaria penetrate walls of lymphadenitis, & lymphangitis
lymphatics → enter adjacent small blood vessels/ carried by lymphatic
b. 4-7 days (with 1-3 recurrences per year)
circulation to the blood stream
c. Funiculitis, epididymitis, orchitis, scrotal
PATHOPHYSIOLOGY edema (hydrocele)
d. Patients do not have microfilaremia
• Granulomatous reaction induced by adult worms in (microfilaria is damaged by the immune
lymphatics reaction)
o Mature worms in lymphatics induce
granulomatous reactions that become • Chronic lymphadenitis with elephantiasis
more pronounced when worms die → a. Develops after years of continuous filarial
occlusion/narrowing of lymphatics → infection
edema b. Damage to lymphatics is caused directly by
• Hypersensitivity to microfilaria adult parasites or by a TH1-mediated immune
o IgE-mediated (in tropical pulmonary response that stimulate granuloma formation
eosinophilia) around the parasites
c. Persistent chronic lymphadenitis & chronic
MORPHOLOGY lymphedema gives rise to fibroblastic
hyperplasia
1. Dilated Lymphatic Vessels in Adult Worms d. The high protein content of lymph stimulates
• Affects Lymphatics of Legs and Genitalia growth of dermal and collagenous connective
tissue →tough subcutaneous fibrosis;
• Thoracic duct/median abdominal lymph
epithelial hyperkeratosis; dilated dermal
vessels →scrotum and penis; external
lymphatics; lymphocytic infiltrates
genitalia in females
(elephantoid skin)
• Inguinal lymph nodes →extremities and
e. No microfilaria because the filaria disappear
external genitalia
after the worms die
• Dilated lymphatic vessels harbouring the
adult worms → causes lymphangitis
• Tropical pulmonary eosinophilia
(inflammation of the blood vessel)
o IgE mediated hypersensitivity reaction to
• Surrounded by mild inflammation
microfilaria: circulating IgE trigger mast cell
(sometimes none), eosinophilia with
degranulation
haemorrhage & fibrosis or granulomas
o Asthmatic episodes at night, with high
2. Lymphedema & Lymph Node Enlargement
peripheral eosinophilia and pulmonary
o Lymph nodes also harbour worms
infiltrates
3. Elephantoid Skin
COMMON TROPICAL INFECTIONS OF THE CVS 5
Dr. Debbi D. de la Fuente
o Eventually results in restrictive lung disease o Blood of patients may not contain
o Microfilariae do not appear in the blood microfilariae in some stages of the disease
because they are trapped in the lungs § It takes 6-12 months from the time of
infection until the worms mature
§ Microfilariae are not found in the early
ASYMPTOMATIC MICROFILAREMIA months of clinical inflammatory
• Moderate lymphadenopathy filariasis and in elephantiasis
• Numerous microfilaria in the blood • Detection of antigen & antibody
• In endemic areas where children are exposed at an o Ags of W. bancrofti – ELISA
early age immunochromatographic test
ACUTE ADENOLYMPHANGITIS OR RECURRENT Brugia Malayi
LYMPHADENITIS • Clinical manifestation are very similar to those of W.
• Sudden onset of high grade fever, painful Bancrofti
lymphadenitis and lymphangitis • More common occurrence of lymphangitis,
• Funiculitis, epidydimitis, orchitis, scrotal edema lymphadenopathy, and abscess-formation in the
• With fever, headache, vomiting, malaise inguinal lymph nodes
• 4-7 days; 1-3 recurrences per year • Elephantiasis is generally confined to the distal
• most patients do not have microfilaremia extremities
o involvement of the external genitalia is not
as common
CHRONIC LYMPHADENITIS WITH ELEPHANTIASIS
• recurrent lmyphangitis results in LEPTOSPIROSIS
o fibrosis • Weil’s Disease, Canicola fever, canefield fever,
o blockage of lymph flow nanukayami fever, 7-day fever
o chronic lymphedema • Invasion across epithelium followed by widespread
• Elephantiasis dissemination to various organs
• Rupture of dlated lymphatics • Direct tissue injury
o Kidney -> chyluria • Induction of mediators
o Tunica vaginalis -> hydrocoele or
chylocoele ETIOLOGIC AGENTS
o Peritoneum -> chylous ascited • Leptospira interrogans (spirochete)
TRANSMISSION
TROPICAL PULMONARY EOSINOPHILIA
• Via infected urine; contaminated water and soil
• IGE-mediated
• Pulmonary inflitrates PATHOPHYSIOLOGY
• Peripheral eosinophilia • Leptospira invades across the mucosa and non-
• Asthma-like attacks intact skin à widespread dissemination (Burrowing
• Microfilaria are trapped in the lungs but rarely action presumably accomplished by axial filaments
demonstrated & release of hyaluronidase)
• Eosinophilic abscess -> granuloma with FB-type
giant cells Mechanisms:
o Near pulmonary venules o Direct tissue injury
o Production of mediators: Endotoxin,hemolysin,
COMPLICATIONS lipase, cytokines
• Superimposed streptococcal infection (Acute
Dermatolymphangioadenitis) SPECTRUM OF DISEASE
• Cellulitis local pain & swelling, fever & chills 1. Anicteric (mild) Leptospirosis (90%)
• Septicemic Phase (4-7 days)
DIAGNOSIS o Absrupt onset of symptoms
• History of exposure to mosquitoes in endemic areas § Fever, shaking, chills, headache and
• Clinical manifestations myalgia, abdominal pain, conjunctival
• Demonstration of microfilariae suffusion
§ Less often: transient skin rash
COMMON TROPICAL INFECTIONS OF THE CVS 6
Dr. Debbi D. de la Fuente
o Septicemic pahse is followed by 2-3 days hemoptysis and pneumonia
of defervescence Kidney • Acute tubular necrosis à kidney
• Immune Phase (4-30 days; ave 14) failure
o Hallmarks: Aseptic Meningitis and Renal • Interstitial nephritis
Dysfunction • Petechial lesions on the surface
o Developmenet of antibodies (appearance Heart • Epicardial & endocardial petechiae
of IgM in serum) • myocardial edema
o Leptospire settle in glomeruli and are
• myocarditis
eliminated from all sites except the eyes
• coronary arteritis
and brain
o Fever and other constitutional symptoms
RES • Hyperplasia
may recur Muscle • Myositis; hemorrhage into muscle
o Leptospire from urine only beds = Rhabdomyolysis
2. Weil’s Disease (10%) – Icteric Leptospirosis Skin • Urticarial, petechial or
• Icteric leptospirosis desquamative lesions
• Usually casued by L. icterohaemorrhagiae CNS • Meningitis
• Persistent fever obscures the biphasic course Eyes • Acute Phase = vasodilation,
• Characterized by: subconjunctival hemorrhage, retinal
o Hepatic dysfunction (jaundice) vasculitis à suffesion (reddening of
o Renal failure (diffuse tubulointerstitial the eye surface)
nephritis, tubular necrosis) • Immune Phase = Iridocyclitis
o Hemorrhage (petechiae, purpura, GIT • Acalculous
conjunctival hemorrhage, GIT • Cholecystitis
hemorrhage) • Pancreatitis
o Multi-organ failure • GI bleeding
3. Sever Pulmonary Hemorrhagic Syndrome
• Hemoptysis, patchy lung inflitrates on x-ray,
respiratory failure (ARDS, total lung PHYSIOLOGIC CONSEQUENCES
consolidation) • Bleeding à anemia
• Renal failure
Note: Immune phase, detected via Urine while septicemic • Third spacing of fluids (due to increased
phase is detected via Blood permeability) à hypovolemia & vascular collapse
• ARDS
MORPHOLOGY
• Capillary Vasculitis (most consistent pathologic SCHISTOSOMIASIS
finding; Increased permeability) & leakage
o Endothelial edema, necrosis, and ETIOLOGIC AGENTS
lymphocytic inflitration • S. japonicum
• Leakage • S. mansoni
o Intraparenchymal bleeding • S. haematobium
o Petechiae
o Bleeding along serosa and mucosa INTERMEDIATE HOST
• Oncomelania (snail)
Organ/Organ Findings
System
Liver • Vascular congestion &
disorganization of the liver cell
plates
• Erythrophagocytosis by Kupffer cells
• Minimal necrosis of hepatocytes à
Jaundice; Hepatitis
Lungs • Alveolar capillary injury à edema;
bleeding (interstitial & intra-
alveolar hemorrhage) à cough,
COMMON TROPICAL INFECTIONS OF THE CVS 7
Dr. Debbi D. de la Fuente
LIFE CYCLE 3. Immunologic process resulting from cumulative
deposition of eggs
• Periportal fibrosis (Pipestem Fibrosis)
• Portal hypertension
o Congestive splenomegaly
o Varices
o Ascites
• Lungs
o Granulomatous pulmonary arteritis ->
poulmonary hypertension
• Heart – cor pulmonale
MORPHOLOGY
• Liver
o Portal fibrosis (pipestem fibrosis, Symmer’s
fibrosis)
Figure 3: Life cycle of Schistosomiasis • Spleen
o Congestive splenomegaly
Summary of Life Cycle
• Portal hypertension
1. Miracidium hatches out from excreted egg
2. Miracidia infect snails o Congestive splenomegaly
3. Cercariae is released from the infected snail o Esophageal varices
4. People are infected by contact with cercariae in water o Ascites
5. Cercariae enters skin and lose their tail to become o Hemorrhoids
schistosomulea • Lungs
6. Schistosomulea migrate through tissues, penetrate a o Granulomatous pulmonary arteritis with
blood vessel
intimal hyperplasia and obstruction ->
7. Brought to right heart and lungs
8. They squeeze through pulmonary capillaries into the pulmonary hypertension
systemic circulation portal vessels • Heart
9. Schistosomulea migrate in the hepatic portal venules o Cor pulmonale
and form pairs • Kidneys
10. Worm migrate against portal blood flow and deposit o Mesangioproliferative or membranous
egss into the mesenteric, vesical and pelvic venules
glomerulonephritis
PATHOPHYSIOLOGY (HOST RESPONSE) • Colon
• Much of the pathology is caused by host o Inflammatory patches or pseudopolyps
inflammatory reactions to the different stages of • Urinary bladder
the parasite o Hyperemia; vesicular or papular mucosal
1. Developmental stage (cercarial penetration to elevations
maturation of adult worms)
o Polyposis
• Transient itching and mild skin rash at area of
cercarial penetration o Calcific sandy patches
• Katayama fever o Ulcers
o Acute systemic illness 2 weeks after heavy o Contraction
exposure (fever, chills, weight loss, o Obstructive uropathy → UTI: due to
weakness, cough) inflammation and fibrosis of the ureteral
2. Period of active oviposition and egg excretion
walls
• Granulomas develop around the egg
• Egg secretes proteases and evoke local o Squamous metaplasia and dysplasia
inflammatory response o Squamous cell carcinoma (S. haematobium)
• Adult worms can cover themselves with host
protein hence immune system does not recognize
them