PATHOLOGY

2.03i Infectious Diseases – Lab Manual

OUTLINE
I. Abscess Brain
II. Purulent Meningitis
III. Bronchopneumonia
IV. Tuberculosis, Lungs
V. Tuberculous Meningitis, Brain
VI. Viral Diseases
A. Interstitial (Viral) Pneumonia
B. Encephalitis, Brain
VII. Mycotic Infection
A. Maduromycosis, Foot
B. Blastomycosis
VIII. Protozoan Diseases
A. Amebiasis, Colon
B. Malaria, Liver
IX. Schistomiasis
A. Schistomiasis, Liver
X. References
I. ABSCESS, BRAIN (#26)
An autopsy was done on an immunocompromised 30-year-old HIV
positive male, who was admitted because of fever, severe
headache, episodes of seizure, and increasing drowsiness. His
condition deteriorated and he eventually died. Pathologic
examination of the brain showed multiple abscesses.
1. Define abscess. What is the expected gross appearance of
the lesion?
• An abscess is a localized collection of purulent inflammatory
tissue. Gross appearance of the lesion would show the
lesion filled with pus, indicating liquefactive necrosis with
fibrosis and inflamed tissue.
2. Differentiate abscess from pus.
• Pus is a purulent exudate consisting of neutrophils, liquefied
debris of necrotic cells and edema fluid while an abscess is
a collection of pus in a cavity within an organ, usually
because of an infection.
3. From your examination of the slide, what part of the brain is
involved (meninges or brain substance)? What type of
exudate is this? What are the inflammatory cells involved in
this type of exudative reaction?
• The brain substance is involved. This is a purulent exudate.
Initially, the inflammatory cells involved in this reaction are
neutrophils, followed later on by monocytes. 
 adolescents and young adults, older adults/elderly).
4. Enumerate the possible routes of entry of the infectious
agent into the intracranial compartment. Correlate the route
with the pathogenesis of brain abscess.
• The possible routes of entry of the infectious agent are:
o direct implantation through surgical procedures
o local extension from adjacent foci (such as mastoiditis,
paranasal sinusitis, otitis media, dental infections)
o hematogenous spread of bacteria from another site of
infection in the heart, lungs, or other organs.
• Head trauma or surgical procedures, inflammation of nearby
tissues, and hematogenous spread can introduce cerebritis
development and capsule formation of the abscess. 

5. Enumerate and explain the clinical signs and symptoms
presented in this case.
• Fever, headache, episodes of seizure, and increasing
drowsiness are the common symptoms seen. These signs
and symptoms arise from the increased intracranial pressure
caused by the growth of the abscess taking up space in the
brain.
6. Give any diagnostic procedure/test which can be used to
aid in the diagnosis of this disease. State the expected
result.
• A brain and nervous system (neurological) exam will usually
show signs of increased intracranial pressure and problems
with brain function.
• A cranial CT scan will show the presence of abscesses in
the brain.
• CSF analysis will show typical composition in brain
abscesses.
• Other diagnostic tests include: blood cultures (for identifying
the causative agent), CHEST X- RAY, CBC, EEG and MRI
of the head.
7. Give the characteristic CSF (cerebrospinal fluid findings)
in this disease.
• Increased WBC count, increased protein concentration, and
normal glucose levels. There is an increase in pressure of
the CSF.
II. PURULENT MENINGITIS (#33)
A 16-year-old female was brought to the ER because of fever,
headache, photophobia and neck stiffness. A lumbar tap done
showed a purulent cerebrospinal fluid (CSF) with increased
pressure; 95% neutrophils/ul; an increased protein concentration
and reduced glucose level. Gram stain of the CSF showed gram-
negative diplococci.
1. What is the expected gross appearance of the lesion?
• The lesion appears as a creamy, purulent exudate that
surrounds the cerebral hemispheres spreading to the
meninges.
2. From your examination of the slide, what part of the brain is
involved (meninges or brain substance)? What type of
exudate is this? What are the inflammatory cells involved in
this type of exudative reaction?
• The part of the brain involved is the meninges, such as
the arachnoid mater and the dura mater. A purulent
exudate is seen composed of inflammatory infiltrates
(neutrophils accompanied by fibrin exudate).
3. Tabulate the most common organism/s which affect the
different age groups (neonates, infants, children,
Age Group Organism
Neonates E. coli, Group B
Streptococcus
Infants Haemophilus influenzae
Children Neisseria meningitidis,
Haemophilus influenzae,
Streptococcus pneumoniae
Adolescents/young adults Neiserria meningitidis
Older adults/elderly Listeria monocytogenes,
Streptocococcus pneumoniae
4. Enumerate and explain the clinical signs and symptoms
arising from the pathology.
• Signs and symptoms: headache, irritability, photophobia,
clouding of consciousness, and stiff neck. Increased
intracranial pressure damages the brain and spinal cord
by pressing on important structures, causing ischemia and
clinical signs and symptoms.

TRANSCRIBERS Reyes, B., Reyes, O., Reyes, R., Reyes, S. EDITOR PIOCNACIA 09262616700 of
1 7
5. Give any diagnostic tool or maneuver which will aid in the 4. Knowing the gross and microscopic findings, list down,
diagnosis of this disease. State the expected result. explain, and correlate the expected clinical signs and
• Spinal Tap – Cloudy or purulent CSF, under increased symptoms arising from the lesion.
pressure, increased protein concentration, reduced • Abrupt onset of high fever, shaking chills, and cough
glucose content. producing mucopurulent sputum
• CSF analysis will show the chemical composition of any • Occasional patients may have hemoptysis.
change in glucose and protein causing edema/swelling. • When pleuritis is present it is accompanied by pleuritic pain
• Lumbar puncture will gauge increased intracranial pressure. and pleural friction rub.
5. Give any laboratory test that would help you in the
6. Give the characteristic CSF (cerebrospinal fluid) findings in diagnosis and expected result.
this disease. • Pulse oximetry <90-92% (hypoxia)
• Decreased glucose concentration, increased protein • Elevated C-reactive protein
concentration, increased neutrophil count, and cloudy • CBC count with differential – leukocytosis
purulent exudates. • Elevated international normalized ratio (INR)
• Single predominant microbe noted at Gram Stain

III. BRONCHOPNEUMONIA (#36)
• Chest x-ray – used to determine extent and location of
An elderly male sought consult because of fever, chills, and cough
infection (radiopaque densities)
with a mucopurulent discharge. Chest x-ray done showed
radiopaque densities consistent with lobar pneumonia. Gram stain
6. What are the expected chest x-ray findings in lobar
of the sputum showed gram-positive, lancet-shaped diplococci.
pneumonia? In broncho-pneumonia?
1. Describe microscopic findings which you see on the glass • Lobar pneumonia – homogenous opacification in a lobar
slide. pattern. The opacification can be sharply defined at the
fissures, although more commonly there is segmental
• Neutrophil infiltration in bronchi and bronchioles, thickened
consolidation
alveolar septa.
• Bronchopneumonia – multiple, small, nodular or
2. Tabulate the etiologic agent, characteristic gross and reticulonodular opacities which tend to be patchy and or
microscopic findings in bronchopneumonia, lobar confluent. Those represent areas of lung where there are
pneumonia and interstitial pneumonia. patches of inflammation separated from normal lung
parenchyma. Distribution is often bilateral and asymmetric
and predominantly involves lung bases.
Broncho Lobar Interstitial
pneumonia Pneumonia Pneumonia
7. What are the complications of lobar pneumonia?
Etiologic Most commonly Most commonly Most
• Meningitis, pleuritis, sepsis, permanent scarring of the lungs,
Agent bacterial (ex. bacterial (ex. commonly
respiratory failure
Pseudomonas Streptococcus viral (ex.
• Spread of infection to the pleural cavity, causing the
aeruginosa, S. pneumoniae) Mycoplasma
intrapleural fibrinosuppurative reaction known as empyema
aureus, K. pneumoniae)
pneumoniae) • Tissue destruction and necrosis
Gross • Bacteremic dissemination to the heart valves, pericardium,
• Patchy • Fibrino- • Honeycomb
Features kidneys, spleen or joints, causing metastaic abscesses,
distribution of suppurative change
endocarditis, meningitis or suppurative arthritis
inflammation • Consolidation affecting
• Involves of a large predominan
more than portion of an tly IV. TUBERCULOSIS, LUNGS (#42)
one lobe entire lobe peripheral A 70-year-old female from Payatas was brought to the OPD
• Usually in and lower because of chronic cough, weight loss, low-grade fever occurring in
basilar parts lung zones the late afternoon, and night sweats of several months duration. A
Microscopic • Neutrophil • Alveolar lumen • Septal chest x-ray showed cavitation of the apex of the right lobe. Acid-fast
Features infiltration in with thickening stain of the sputum showed acid-fast bacilli.
bronchi and neutrophils • Dense
bronchioles and eosinophilic 1. What is meant by miliary tuberculosis? Cavitary
• Thickened macrophages collagen tuberculosis?
alveolar septa • Thickened desposition • Miliary tuberculosis is characterized by a multitude of
alveolar walls • Fibroblastic small, pale tan granulomas (resembling millet seeds),
• Congested foci brought upon by a poor immune response, or an extensive
capillaries infection. With it, organisms draining through the lymphatics
enter the venous blood and circulate back to the lung.
3. Discuss the pathogenesis of broncho- and lobar • Cavitary Tuberculosis is characterized by extensive
pneumonia. necrosis with cavitation, occurring usually in the upper lung
• Often, the bacterial infection follows an upper respiratory lobes. It produces cavities in infected tissue. It is the
tract viral infection.Initial terminal bronchiolitis with patchy characteristic feature of secondary tuberculosis. Its
consolidation of peribronchial lung tissue à bronchioles are cavitations are due to involvement of walls of the airways.
plugged by swollen mucosa and their secretions à air
cannot enter the alveoli à imprisoned air in the alveoli is 2. Give the gross appearance of miliary pulmonary
absorbed à collapse of the alveoli à collapsed areas are tuberculosis and cavitary lung tuberculosis.
surrounded by areas of compensatory emphysema à
resolution of the exudates usually restores normal lung
structure à organization may occur à fibrosis/scarring in
some cases à aggressive disease may produce abscesses

of
2.03g INFECTIOUS DISEASES - MANUAL 2 7

Figure 1. Miliary Tuberculosis
• Miliary tuberculosis - a multitude of small, pale tan
granulomas (resembling millet seeds), averaging between 2
to 4 mm in size, scattered throughout the lung parenchyma
Figure 2. Secondary/Cavitary Tuberculosis
• Cavitary Tuberculosis – extensive necrosis with
cavitation occurring usually in the upper lung loves
3. What is a tubercle? What are its components?
• It is a granulomatous lesion due to infection by M.
tuberculosis. They tend to be well circumscribed, spheroid,
and firm lesions that consist of an area of caseous necrosis
made up of modified macrophages (epithelioid cells),
surrounded by a rim of mononuclear cells (lymphocytes), and
sometimes a cluster of giant cells (Langhans giant cell).
4. Knowing the gross and microscopic findings of pulmonary
tuberculosis, enumerate the clinical signs and symptoms
related to the pathology.
• General malaise, weakness, fever, hemoptysis (coughing of
blood), weight loss, anorexia
5. Discuss the pathogenesis of disseminated tuberculosis.
• Following exposure and inhalation of TB bacilli in the lung, a
2.03g INFECTIOUS DISEASES - MANUAL
primary pulmonary complex is established, followed by
development of pulmonary lymphangitis and hilar
lymphadenopathy. Mycobacteremia and hematogenous
seeding occur after the primary infection. After initial
inhalation of TB bacilli, miliary tuberculosis may occur as
primary TB or may develop years after the initial infection.
The disseminated nodules consist of central caseating
necrosis and peripheral epithelioid and fibrous tissue.
Radiographically, they are not calcified (as opposed to the
initial Ghon focus, which is often visible on chest
radiographs as a small calcified nodule).
6. What laboratory tests would help you in the diagnosis of
the disease? Give the advantages and disadvantages of
these tests.
Diagnosis of tuberculosis can be aided by:
• Interferon-Gamma Release Assay
o Advantages: Results are faster compared to skin test. It
is also preferred over skin test for people who have
received TB vaccine BCG.
o Disadvantage: It may not be available in rural areas.
• Tuberculin Skin Test
o Advantages: Could be repeated as many times as
needed. If repeated, the additional test should be done
on a different location on the body, (e.g., the other arm).
It is also the preferred test for children under the age of
5.
o Disadvantages: The patient needs to come back 2 – 3
days after the tuberculin injection to determine if he / she
is positive for the test.
• Chest Radiograph
o Advantages: Available in almost all hospitals, even in
rural areas
o Disadvantages: Etiology is difficult to ascertain; shadow
could be mistaken for pneumonia if doctor is not careful.
7. What are the complications of pulmonary tuberculosis and
the mechanism of their production?
• Immune reconstitution inflammatory syndrome (IRIS): Also
known as a paradoxical response. It involves transient
worsening of TB symptoms and lesions following initiation of
anti-TB therapy. This is much more common in HIV- positive
patients with severe immunosuppression who are placed on
antiretroviral (ARV) therapy.
• Pneumothorax: Results from rupture into the pleural space of a
peripheral cavity or of a subpleural caseous focus that has
liquefied. The associated bronchopleural fistula (BPF) may seal
off or persist. Large BPF may lead to empyema formation.
• Empyema: May be seen in primary disease but usual
presentation is in the setting of extensive parenchymal disease.
• Bronchiectasis: May result from primary TB, distal to the site of
obstruction if adenopathy causes bronchial compression. If
reactivation causes parenchymal destruction, bronchiectasis
may develop in area of involvement.
• Extensive lung destruction: Extensive pulmonary parenchymal
destruction may occur in primary or reactivation TB. Pulmonary
destruction is usually the result of chronic, progressive,
untreated pulmonary TB.
• Hemoptysis: TB accounts for less than 10% of cases of
hemoptysis. It may be seen in active or treated disease and is
usually small in volume.
of
3 7
 V. TB MENINGITIS, BRAIN (#52) • Papovavirus – affects oligodendrocytes à loss of myelin in
A 12-year-old male complains of headache and fever of two weeks white matter à multifocal leukoencephalopathy
duration. The mother notices that her son was getting sleepy and • Tick-borne virus – In the first phase, it causes leukopenia
unarousable. He was brought to the hospital. Neck rigidity was and thrombocytopenia. By the second phase (onset of
elicited. neurologic disease), there is an increase of WBC in blood
and CSF.
1. Describe the gross appearance of tuberculous meningitis. • Mosquito-borne flavivirus - Direct invasion of the virus into
Correlate the clinical manifestation presented, vis-à-vis with the nervous system, selective infection and destruction of
the gross features of this disease. neurons, and evidence that both humoral and cellular
• Grossly, there are whole granules scattered in the meninges immune responses attenuate the infection.
and fibrinous exudates are seen in the subarachnoid space 3. What laboratory tests would help you in the diagnosis of
at the base of the brain, thus obliterating the arteries and viral encephalitis?
encasing the cranial nerves. The response and symptoms of • Ab probes, MRI, CT scan, DNA probes, Culture, H & E stain,
the patients occur due to the tension/strain caused by the EEG, Tissue biopsy.
inflamed meninges. 4. Tabulate the different CSF findings in acute bacterial
meningitis, brain abscess, viral encephalitis, fungal
2. Describe the histopathologic features of the lesion as seen (cryptococcal) meningitis.
in the slide.
• Chronic inflammatory reaction: lymphoplasma cells and Acute Fungal
Brain Viral
macrophages Bilateral (cryptococcal
abscess Encephalitis
• Well-formed granuloma with central caseous necrosis Meningitis ) meningitis
surrounded by epithelioid cells and giant cells
Opening
• Gliosis pressure
↑ ↑ ↑ ↑
• Calcification in inactive area

3. Give the characteristics CSF findings in Tuberculous

meningitis. Number ↑ ↑ Few:
and type of ↑ Neutroph Lymphocytes Lymphocytes
• Moderate pleocytosis (mononuclear cells or mixture of &
inflammatory Neutrophils ils/ w/
mononuclear cells and PMN) cells WBC neutrophils macrophages
• Elevated protein content
• Normal or reduced glucose level
Protein ↑ ↑
↑ ↑
VI. VIRAL DISEASES level moderate concentration
A. Interstitial (Viral) pneumonia (Slide #40) Sugar ↓ Nearly
Normal —
1. Describe the microscopic features of interstitial (viral) level Glucose normal
pneumonia and differentiate it from bacterial pneumonia.
• Interstitial (viral) pneumonia is seen to be bluish-red with Sugar level
alveolar spaces with edematic fluid and smooth pleura. in
Nearly
There is congestion and a pink hyaline membrane lining the comparison ↓ Normal —
normal
alveolar walls, with the latter remaining to be intact while with blood
bacterial pneumonia is simply an infiltration of alveolar sugar level
space.

2. What virus(es) is/are usually involved? Give the
pathogenesis.
• Rhinovirus – injury to epithelial cells, release bradykinin à
↑mucus secretion à IgA, IgG formation prevents reinfection
• Influenza – haemagglutination binds salicylic acid containing
glutan and lipids for host cells à entry to cell endosome à
fuse to cytosome à conformational change à salicylic acid
removed à release from host cells
B. Encephalitis, brain (Slide #29)
1. Describe what you see in the microscope, noting the blood
vessels and its immediate surrounding, brain parenchyma,
and meninges.
• Brain parenchyma – perivascular mononuclear infiltration
• Meninges – eosinophilic viral inclusion bodies with
perivascular cuffing by lymphoid cells
• Encephalitis – lymphocytes and BV with plasma cells,
macrophages, glial cells or modules
2. Enumerate at least 5 viruses that can cause encephalitis?
Give the pathogenesis.
• Rabies virus – neutrotropic; results in meninges encephalitis
with virus inclusions visible in neuronal cells
• Herpes virus – causes severe form of generalized
encephalitis; extensive necrosis of brain tissues
VII. MYCOTIC INFECTION
A. Slide #53 – Maduromycosis foot (Demo slide)
1. Describe the histopathologic findings, taking special
interest on the characteristic appearance of the organism
and the type of exudates.
• Microorganism appears intracellularly with brownish color.
The dermis and subcutaneous tissue contain localized
abscesses, each of which contains one or more granules
in its center. Eosinophilic, club-like, Splendore-Hoeppli
material may border the granules. Between abscesses,
there is extensive formation of granulation tissue, resulting
in tumefaction and deformity that is often so severe as to
be mistaken clinically for a neoplasm.
B. Blastomycosis (Demo slide)
1. What is the expected gross appearance of this lesion?
• Multiple suppurative granulomas scattered throughout the
parenchyma.
2. What is the reason for the characteristic gross
appearance of the pulmonary lesion in this type of fungal
infection?
• Failure of macrophages to kill invading microorganisms,
leading to continued recruitment of neutrophils.

of
2.03g INFECTIOUS DISEASES - MANUAL 4 7
 3. Describe the microscopic findings which you see on the • E. Histolytica is resistant to complement-mediated lysis
glass slide. (survival), degradation of collagen, elastin, IgA, IgG, C3a &
• Tissue section showing large, broad-base, and unipolar C5a
budding yeast-like cells. • Lysis of neutrophils, monocytes, Iymphocytes, cells of colonic &
hepatic lines
VIII. PROTOZOAN DISEASES • Cytolytic effect (contact with target cells and linked to release
A. Amoebiasis, Colon (Slide #67, Demo Slide) of PLA & pore-forming peptides)
1. Describe the characteristic gross appearance of amebic • Cause apoptosis of human cells, phagocytosis
ulcer. • Thioredoxin reductase system to prevent, regulate, & repair the
• In the early stages, colonic ulcers have a narrow neck and damage caused by oxidative stress (resist ROS and RNS)
thus appear as small nodules with a minute surface
opening (5 mm in diameter). As the ulcers enlarge, they 4. Give the expected clinical signs and symptoms and
retain their undermined base but the ulcerated area of the complications related to the lesion. What laboratory test(s)
mucosa becomes larger. Muscle coat of the large intestine would aid in the diagnosis?
form a barrier to the penetrating trophozoites which fan out • Clinical signs and symptoms:
laterally producing a flask-shaped ulcer with narrow neck o Lower abdominal pain followed by diffuse back pain
and broad base. The base of the ulcer is covered by grey - o Mild diarrhea followed by malaise and weight loss
white exudate. Therefore, typical endoscopic appearance o Full blown dysentery may pass 10-12 stools per day
of amoebic colitis appears as small discrete areas of o Few fecal material, presence of more blood and mucous
ulceration with normal intervening mucosa. • Laboratory Tests:
o Stool examination
2. Describe the microscopic feature of the lesion. State the o Serologic test
type of inflammatory cells accompanying the lesion. o Non-invasive imaging of the liver
• The eroded mucosal layer forming the ulcer appears flask- o Ultrasonography
shaped with a broad base and narrow neck. Granulation o CT Scan
tissue, fibrosis, inflammatory cells (neutrophils, o MRI
lymphocytes, histiocytes, plasma cells and sometimes • Complications:
eosinophils) and clusters of trophozoites concentrate in o Brain Abscess
the submucosa. o Lung Infection
o Liver abscess
3. Give the pathogenesis of amoebic colitis from ingestion of o Sub-diaphragmatic and sub-hepatic infections
the infective stage to the development of the ulcers to its o Periappendiceal infection
different complications. o Colon Ulcers (Amoebic ulcers)
o Peritonitis
o Amoeboma
o Anorectal fistula
o Cutaneous amoebiasis
o Pericardial effusion, amoebic pericarditis

B. Malaria, liver (Slide #63)

1. Describe the morphologic changes in these different
organs brought about by malaria.
a. Liver
• Becomes progressively enlarged (hepatomegaly)
and pigmented. The kupffer cells will take up the
parasitized RBC, the parasites and hemozoins

• Route: fecal route

Short version: E. histolytica cysts which have a chitin wall, 4 nuclei

are the infections formed because they are resistant to gastric acid.
In the colonic lumen, cysts release trophozoites. The amoeboid then
becomes reproductive and multiply in the colon. They attach to the
colonic epithelium and they lyse colonic epithelium cell.

Long version:
• Only the trophozoites can invade tissue
• Depletion of intestinal mucus, diffuse inflammation, & disruption
of the epithelial barrier (precede contact) Figure 3. Liver infected by malaria (Gross)
• Trophozoites attach to colonic mucus & epithelial cells b. Spleen
(Gal/GalNAc lectin) causing microulcerations of the mucosa of • Infection initially causes congestion and enlargement
cecum, sigmoid colon, rectum seen as pin prick lesions of the spleen (splenomegaly) which is caused by
(earliest lesion) macrophages phagocytosing parasites and
hemozoin.
• Liver abscesses are always preceded by intestinal colonization
• Blood vessels may be compromised early by wall lysis &
c. Brain
thrombus formation, trophozoites invade veins to reach liver
• Infected RBCs clump together forming rosettes and

of
2.03g INFECTIOUS DISEASES - MANUAL 5 7
 stick along the endothelial lining of the blood vessels
in the brain resulting to hemorrhages, vascular
stasis, clogging of lumen of blood vessels which then
leads to poor perfusion leading to hypoxia, ischemia
and infarction of the brain.
2. What pigment accumulation is noted in malaria? How is the
pigment produced? What is the expected Prussian blue
reaction?
• Malaria/ Hemozoin pigment.
o RBCs are parasitized causing degradation of
hemoglobin and subsequent release of heme. Heme is
then converted into an insoluble crystalline thereby
producing a hemozoin.
o It will have (-) Prussian blue reaction since the iron
found in the pigment is in ferric form making it
nonreactive.
3. Give the pathogenesis of malaria and the different organs
affected as the organisms multiply.
• An anopheles mosquito bites a human (injecting the
sporozoites) and sucks human blood. Sporozoites will be
inoculated in the blood stream. Some will leave the blood
enter the hepatocytes and multiply asexually (exo-
erythrocytic) to form uninucleated merozoites. When the
hepatocyte ruptures, it will release thousands of merozoites
that will penetrate the red blood cells next and become
trophozoites. Trophozoites will divide and form schizonts
(intraerythrocytic). Schizonts divide,form several merozoites,
which are released on ruptured erythrocytes, reenter
erythrocytes and begin another cycle. After several cycles,
merozoites develop into macrogametocytes (ovum) and
microgametocytes (sperm). These gametocytes are taken
by the mosquito, undergo sexual reproduction and produce
the infective sporozoites.
Figure 4. Life cycle and Pathogenesis of Malaria.
4. Why does Plasmodium falciparum cause a more severe
disease compared with other malarial parasites (P. vivax, P.
ovale and P. malariae)?
• Plasmodium falciparum is the most virulent because it
replicates quickly in the blood and affects both young and old
RBCs.
• Plasmodium falciparum causes more severe disease than the
other Plasmodium species do. Several features of P.
falciparum account for its greater pathogenicity (Robbins):
o P. falciparum is able to infect red blood cells of any age,
whereas other species infect only young or old red cells,
which are a smaller fraction of the red cell pool.
2.03g INFECTIOUS DISEASES - MANUAL
o P. falciparum causes infected red cells to clump together
(rosette) and to stick to endothelial cells lining small blood
vessels (sequestration), which blocks blood flow. Several
proteins, including P. falciparum erythrocyte membrane
protein 1 (PfEMP1), associate and form knobs on the
surface of red cells. PfEMP1 binds to ligands on
endothelial cells, including CD36, thrombospondin, VCAM-
1, ICAM-1, and E-selectin. Red cell sequestration
decreases tissue perfusion and leads to ischemia, which is
responsible for the manifestations of cerebral malaria, the
major cause of death in children with malaria.
o In P. falciparum infection, GPI-linked proteins, including
merozoite surface antigens, are released from infected red
cells and induce cytokine production by host cells. These
cytokines, including TNF, IFN-γ, and IL-1, suppress
production of red blood cells, increase fever, stimulate the
production of reactive nitrogen species (leading to tissue
damage), and induce expression of endothelial receptors
for PfEMP1 (increasing sequestration).
IX. SCHISTOSOMIASIS (Slide #57)
A 35-year-old male farmer from Southern Leyte, was admitted due to
progressive ascites.
1. Give the pathogenesis involved in liver schistosomiasis.
• Schistosoma eggs trapped → antigen release → granulomatous
necronium with T cells, macrophage and eosinophils → Th2
cells produce IFN4 →> macrophage secretes TNF, IL1, IL6 →
fever
• The eggs of the schistosoma will elicit an inflammatory response
→ granuloma formation and fibrosis → liver cirrhosis
• The helper T-cell response in the early stage is dominated by
TH2 cells that produce INFy which stimulates macrophages to
secrete high levels of cytokines TNF, IL-1 and IL6 that causes
fever. Chronic schistosomiasis is associated with a dominant
TH2 response, associated with the presence of alternatively
activated macrophages. Both types of helper T cells contribute
to the formation of granulomas surrounding eggs in the liver.
2. How does parasitic (pipe-stem) cirrhosis develop?
• In late S. mansoni or S. japonicum infections, inflammatory
patches or pseudopolyps may form in the colon. The surface of
the liver is bumpy, and cut surfaces reveal granulomas and
widespread fibrosis and portal enlargement without intervening
regenerative nodules. Because these fibrous triads resemble
the stem of a clay pipe, the lesion is named pipe-stem fibrosis.
• The fibrosis often obliterates the portal veins, leading to portal
hypertension, severe congestive splenomegaly, esophageal
varices, and ascites. Schistosome eggs, diverted to the lung
through portal collaterals, may produce granulomatous
pulmonary arteritis with intimal hyperplasia, progressive arterial
obstruction, and ultimately heart failure (cor pulmonale).
Figure 5. Parasitic fibrosis, liver. Pipe stem fibrosis of liver due
to chronic Schistosoma sp. infection. Cut surface shows
granuloma and widespread fibrosis and portal enlargement
intervening regenerative nodules (Red: Portal enlargement;
green: granuloma; purple: fibrosis)
of
6 7
 REFERENCES
3. Review and draw the life cycle of Schistoma japonicum 1. 2019 Transcriptions.
organism. 2. Robbins.
• The eggs will be deposited in the submucosal/mucosal 3. Robbins Atlas.
terminal vein.
• They then escape through ulcerations into intestinal lumen
and are exported with feces.
• Eggs will hatch into free-swimming ciliated miracidium (pl.
miracidia), which will penetrate the snails.
• Inside the snail, 1st and 2nd generations of sporocysts will
be formed and within the daughter sporocyte, the cercaria
will emerge and escape into surrounding waters.
• Cercaria will swim on surface water and will infect host/s via
penetration of the skin.
• After penetration cercaria will transform into the
schistosomulum (pl. schistosomulae), which enters the
lymphatic vessels →subcutaneous veins to reach the lungs
→ liver → intrahepatic portions of portal vein.

Figure 6. Life cycle of Schistosoma japonicum

4. Differentiate the immune response/s involved in an acute

schistosomiasis from that of chronic schistosomiasis.
• Acute Schistosomiasis
o Dominated by Th1 cells
o Production of IFN gamma will stimulate macrophages and
thus pyogens production
o Accompanied by severe febrile illness that peaks 2 months
after infection
• Chronic Schistosomiasis
o Dominated by Th2 cells
o Proteins in parasite ova cause mast cells to produce IL4
which induces TH2 differentiation

of
2.03g INFECTIOUS DISEASES - MANUAL 7 7