3.

01

January 6,
2017

BLOOD AND TISSUE NEMATODES

Dra. Nacpil

Department of Parasitology

TOPIC OUTLINE
I.
Filariasis
a. Lymphatic Filariasis
Wuchereria bancrofti
Brugia malayi
b. Loaiasis
Loa loa
c. Mansonelliasis
Mansolnella ozzardi
Mansonella perstans
Mansonella streptocerca
d. Onchocerciasis
Onchocerca volvulus
II.
Trichinosis
Trichenella
III.
Angiostrongyliasis
Angiostrongylus
IV.
Toxocariasis
Toxocaria
V.
Anisakiasis

Female worms produce microfilariae which

circulate in the blood except: O. volvulus (in the
skin and eye) and M. streptocerca (in the
skin)
Inside the arthropod, microfilariae develop in 1-2
weeks into infective filariform (3rd stage) larvae
During a subsequent blood meal by the insect, the
larvae infect the vertebrate host migrate to the
appropriate site and develop into adults, a slow
process that can require up to one month in the
case of Onchocerca

Table 2. Summary of vectors and body parts inhabited

Species
W. bancrofti
B. malayi

Anisakis

Causative agent: Nematodes (round worms) that

inhabit the lymphatics and subcutaneous tissues
8 main species infect humans and 3 of these cause
most of the morbidity due to filariasis: W. bancrofti,
B. malayi and O. volvulus

Mosquitoes

O. volvulus

Blackflies
(Simulium)

L. loa

Deer flies
(Chrysops)
Midges

FILARIASIS

Vector

M.
streptocerca
M. perstans

Midges

Table 1. Geographic distribution of blood and tissue

nematodes

Species
Wuchereria bancrofti
Brugia malayi
Brugia timori
Onchocerca volvulus
Loa loa
Mansonella
streptocerca
Mansonella perstans
Mansonella ozzardi

Distribution
Tropical areas
Asia
Islands of Indonesia
Africa, Latin America,
Middle East
Africa
Africa
Africa, South America
American continent

Life Cycle
Infective larvae are transmitted by infected biting
arthropods during blood meal
Larvae migrate to the appropriate site of the hosts
body, where they develop into microfilariaeproducing adults
Adults dwell in various human tissues where they
can live for several years.
The agents of lymphatic filariasis reside in the
lymphatic vessels and lymph nodes

1 of x

[E na na, whats my name?]

M ozzardi

Midges &
blackflies

Inhabited body
part
Lymphatic vessels
and nodes
Nodules in
subcutaneous
tissue
Subcutaneous
tissue
Dermis and
subcutaneous
Body cavities and
surrounding
tissues
Subcutaneous
tissues

Lymphatic Filariasis

Wuchereria bancrofti
Mosquito vector depends on geographic
distribution most widespread filarial parasite
(India, SE Asia, Pacific islands, Africa, South and
Central America); Philippines: Bicol Region,
Mindoro, Masbate, Romblon, Bohol, Samar, Bontoc,
Sulu, Tawi-Tawi
Adults produce microfilariae which are sheathed
and have nocturnal periodicity (except the South
Pacific microfilariae which have the absence of
marked periodicity)
Anopheles minimus flavirostris principal vector
for malaria in the Philippines also a vector of
bancroftian filariasis in Mt. Province, Sulu, and
Palawan
Aedes poecilus vector in other provinces; breeds
in water accumulated in the axils of abaca and
banana plants
Brugia malayi

Blood and Tissue Nematodes

Palawan, Eastern Samar, Agusan del Sur

coexists with W. bancrofti
Vector is Mansonia bonnae breeds in
freshwater swamps and Mansonia uniformis
breeds in rice fields
Night biters: 5-11pm; Prevalence: 3%
Cats are important reservoir host & transmit
infection to humans by means of catmosquito-man cycle
There are two strains of B. malayi:
1. Nocturnal periodic strain widely
distributed in Asia, the microfilariae being
in their highest concentrations between
10pm to 2am
2. Subperiodic strain in Malaysia,
Indonesia and Philippines where humans
exhibit a microfilaremia all the time with
the highest numbers being detected
between noon and 8pm

Life Cycle (W. bancrofti and B. malayi)

DIAGNOSTIC: microfilariae
INFECTIVE: 3rd stage filarial larvae

A mosquito ingests the microfilariae during a

blood meal (4).
After ingestion, the microfilariae lose their
sheaths and some of them work their way
through the wall of the proventriculus and
cardiac portion of the mosquitos midgut and
reach the thoracic muscles (5).
There the microfilariae develop into 1st stage
larvae (6) and subsequently into 3rd stage
infective larvae (7).
The 3rd stage infective larvae migrate through
the hemocoel to the mosquitos proboscis (8)
and can infect another human when the
mosquito takes a blood meal.

Term

Disease
caused

Vectors

Figure 1. Life cycle of W. bancrofti and B. malayi

During a blood meal, an infected mosquito

introduces 3rd stage filarial larvae onto the
skin of the human host, where they penetrate
into the bite wound (1).
They develop in adults that commonly reside
in the lymphatics (2).
The microfilariae migrate into lymph and blood
channels moving actively through lymph and
blood (3).

Developm
ent of
microfilari
ae
infective
stage
Mean
length
Cephalic
space
(breadth)
Sheath in
Giemsa
Nuclei
Tail

2 of
x

[E na na, whats my name?]

Parasite Biology
W. bancrofti
B. malayi
FILARIAL WORM
Bancrofts filarial
Malayan
worm
filarial
worm
Bancroftian
Malayan
filariasis chronic
filariasis
disfugring disease
chronic
lymphedema,
infection also
elephantiasis,
presents with
hydrocele, chronic
lymphedema
epididymis,
and
thickening of
elephantiasis
spermatic cord
but not as
severe;
enlargement
of
epitrochlear,
inguinal,
axillary
lymph nodes
Aedes, Culex,
Mansonia
Anopheles
6-20 days
2 weeks;
maturation
time for 3rd
stage larvae
adult is 3-9
months
290m
222m
1:1

2:1

Unstained

Pink

Regularly spaced,
separately situated

Irregularly
spaced and
overlapping
Single row of

Single row of

Blood and Tissue Nematodes

Terminal
Nuclei

Appearan
ce in
blood film
Male
Female

Length
Appearan
ce

nuclei that does

not reach the tails
ends
None

Smoothly curved
ADULT
2-4 cm
8-10 cm creamy
white, long, filiform
in shape
MICROFILARIA
270-290m by 67m
Enclosed in hyaline
sheath longer than
the microfilariae
itself; nocturnal
periodicity; central
axis is seen as
composed of dark
staining nuclei;
column of nuclei
are in 2-3 rows and
are distinctly
conspicuous; has
several curvatures;
microfilaria
appears snake-like
in fresh specimens
among RBC

nuclei that
reaches the
tails ends
2 nuclei
which bulge
the cuticle,
conspicuousl
y placed
Kinky

13-23 mm
43-55 mm

177-230m
Enclosed in
sheath; has
angular
curvatures
with
secondary
kinks; has 2
nuclei at the
tip of the tail;
column are in
2 rows which
are indistinct
or confluent

Clinical Manifestations
Lymphatic filariasis most often consists of
asymptomatic microfilaremia
Development of lymphatic dysfunction causing
lymphedema and elephantiasis
With W. bancrofti, there is hydrocele & scrotal
elephantiasis

3 of
x

[E na na, whats my name?]

Febrile lymphangitis and lymphadenitis may

occur
Persons who have newly arrived in diseaseendemic areas can develop afebrile episodes
of lymphangitis & lymphadenitis
Tropical Pulmonary Eosinophilia
Syndrome (TPE)
o An additional manifestation of filarial
infection, mostly in Asia
o Immunologic hyperresponsiveness to filarial
infection
o Characterized by nocturnal cough,
wheezing, fever, and eosinophilia, diffuse
military lesions or increased vascular
markings, high titers filarial antibody (IgE,
good therapeutic response to
Diethylcarbamazine citrate); can progress
to pulmonary fibrosis and respiratory failure
In endemic countries, symptoms may overlap
Microfilariae less pathology associated with
TPE, granulomas of the skin, allergic reactions
following destruction by drugs
Expatriate Syndrome those who are
infected after migration to endemic regions
present with this syndrome; clinical and
immunologic hyperresponsiveness to the
mature or maturing worms; presents with
lymphadenitis and lymphangitis with allergic
reactions such as hives, rashes, and blood
eosinophilia

I. ASYMPTOMATIC STAGE

Presence of thousands to millions of

microfilariae in the peripheral blood and adult
worms in the lymphatic system with no
manifestations of filariasis

Seen among those with highly down regulated

immune state

May have hidden lymphatic pathology and

kidney damage

Brugia can selectively induce CD4+

lymphocyte apoptosis which contributes to
immune system unresponsiveness to filariasis

Also seen in endemic normals who harbor the

parasite antigen in their blood instead of the
microfilariae
II. ACUTE STAGE

Early manifestations: fever, inflammation of

the lymph glands (especially of the male
genital organs, arms, and legs)

Recurrent attacks: swelling and redness of the

arms and legs, accompanied by vomiting and
headache

Blood and Tissue Nematodes

S/sx reflect immunologic phenomenon caused

by sensitization to the products of living or
dead worms collectively called
adenolymphangitis (ADL) or
dermatolymphangioadenitis (DLA)

III. CHRONIC STAGE

With repeated acute episodes, acute

manifestations merge into a chronic
proliferative overgrowth of fibrous tissue
around the dead worms lymphatic
obstruction, recurrent attacks of DLA and
lymphedema, elephantiasis or hydrocele

Cellular reaction and edema are replaced by

fibrous hyperplasia (parasite absorbed and
replaced by granulation tissue, while lymph
varices are produced; increased lymphatic
fluid pressure and high protein content of
lymph stimulate growth of dermal and
collagenous tissue elephantiasis (hard, loss of
skin elasticity, fibrosis)

Develops slowly: chronic pitting edema,

chronic nonpitting, edema with repeated acute
inflammatory episodes
o Lymphedema: 6 months; Elephantiasis:
1 year

In endemic communities different stages

overlap

Manifestations are caused by adult worms,

living, dead, or degenerating

Microfilariae cause less pathology but have

been associated with: TPE, skin granulomas,
allergic reactions following destruction by
drugs

Fig. 3. Wuchereria scrotum

Wuchereria scrotum worms in scrotal

lymphatics stimulates proliferation of lymphatic
endothelium and accumulation of hydrocele fluid
Chyluria rupture of lymphatics in the kidney due
to blockage of retroperitoneal lymph nodes;
several reports of glomerulonephritis in
bancroftian filariasis

Loaisis

Loa loa
African eye worm: Sudan rainforest, basin of
Congo and W. Africa
Causes Loaisis: similar to onchocerciasis and
can cause blindness
Migrates throughout subcutaneous tissues of
the body
Most conspicuous and irritating when crossing
the conjunctiva

Fig.4 L. loa microfilariae (L) and its vector, Chrysops (R )

Fig. 2. Wuchereria elephant foot

Wuchereria Elephant foot increased

lymphatic fluid pressure and high protein content
of lymph stimulate growth of collagenous CT;
enlarge parts hidden with loss of skin elasticity
and fibrosis producing elephantiasis

Vectors: Chrysops silacea and C. dimidata

(deerflies), both are day-biting flies
Adult males: 2-3.5 cm long ; Adult females: 57cm long
Microfiariae: 250-300 um long, sheathed and
have body nuclei that are continuous to the tip
of the tail (difference to that of Wuchererias &
Brugias microfilariae
Microfilariae has diurnal periodicity
o During the day peripheral blood
o During the non-circulation phase
lungs
Microfilariae have been recovered from spinal
fluids, urine, and sputum
Life Cycle

4 of
x

[E na na, whats my name?]

Blood and Tissue Nematodes

DIAGNOSTIC: microfilariae
INFECTIVE: 3rd stage filarial larvae

During a blood meal, an infected fly introduces

3rd stage filarial larvae onto the skin of the
human host, where they penetrate into the
bite wound (1).
The larvae develop into adults that commonly
reside in subcutaneous tissue (2).
Adults produce microfilariae that are found in
peripheral blood during the day but during the
non-circulation phase, are found in the lungs
(3).
The fly ingests microfilariae during a blood
meal (4).
After ingestion, the microfilariae lose their
sheaths and migrate from the flys midgut
through the hemocoel to the thoracic muscles
of the arthropod (5).
There the microfilariae develop into 1st stage
larvae (6) and subsequently into 3rd stage
infective larvae (7).
The 3rd stage infective larvae migrate to the
flys proboscis (8) and can infect another
human when the fly takes a blood meal (1).
Clinical Manifestations
Often asymptomatic
Episodic angioedema & subconjunctival
migration of an adult worm can occur
Non painful migration through tissues
Conjunctival edema
Calabar swelling patches of localized
subcutaneous edema
Eosinophilia

Fig. 5. Calabar swelling (L) and may lead to progressive

keratitis (R )

Mansonelliasis
Mansonella
M. ozzardi
M.
perstans
Vecto
r

Midges
(Culicoides)
or Black
flies
(Simulium)

Midges
(Culicoides)

Adult
s

Females:
65- 81 mm
in length
and 0.21 to
0.25 mm in
diameter
Males:
unknown

Females:70 80 mm in
length and
120 m in
diameter

Females:
27 mm in
length by
50 -85
m

Males: 45
mm by 60
m.
Deep
connective
tissue

Males: 50
m

Unsheathed

Unsheath
ed

No
periodicity
(Doc Nacpil);
Weak diurnal
periodicity
(Doc Malijan)

No
periodicit
y (Doc
Nacpil);
Weak
diurnal
periodicit
y (Doc
Malijan)
Nuclei
extend to
the tip of
the tail
which is
bent in
the form
of a
shepher
ds
crook

Microfilaria
e
Perio
di-city

Tail

Clinic
al

5 of
x

[E na na, whats my name?]

M.
streptoc
erca
Small
midges
(Culicoid
es)

Inhabit
mesenterie
s and
visceral fat
Unsheathe
d
No
periodicity

Nuclei do
Nuclei
not extend
extend until
to the tip of the tip of the
the tail and
tail
tail is
shorter and
less
tapered
than
Onchocerc
a ; button
hook
Found in the blood;
may be obtained by skin biopsy
Generally
Often
Skin
asymptoma asymptomati manifest

Blood and Tissue Nematodes

Manif
estati
ons

tic, inguinal
adenopathy
has been
reported,
skin
lesions,
arthritis,
fever,
marked
eosinophilia
and
pulmonary
symptoms,
adenopathy
,
hepatomeg
aly,
pruritus

c, associated
angioedema,
pruritus,
fever,
headaches,
arthralgias,
and
neurologic
manifestatio
ns; edema
and
inflammatory
changes and
granulomas
from around
dead filariae;
marked
eosinophilia

ations
including
pruritus,
popular
eruptions
and
pigmenta
tion
changes

Life Cycle
DIAGNOSTIC: microfilariae
INFECTIVE: 3rd stage larvae

Life Cycle
DIAGNOSTIC: microfilariae
INFECTIVE: 3rd stage larvae

During a blood meal, the infected vector

introduces 3rd stage filarial larvae onto the
skin of the human host, where they penetrate
into the bite wound (1).
The larvae develop into adults that commonly
reside in the subcutaneous tissue (M. ozzardi),
peritoneal or pleural cavity (M. perstans),
dermis (M. streptocerca) (2).
Adults produce unsheathed and nonperiodic
microfilariae that reach the bloodstream (3).
A vector ingests microfilariae during a blood
meal (4).
After ingestion, the microfilariae lose their
sheaths and migrate from the flys midgut
through the hemocoel to the thoracic muscles
of the arthropod (5).
There the microfilariae develop into 1st stage
larvae (6) and subsequently into 3rd stage
infective larvae (7).
The 3rd stage infective larvae migrate to the
flys proboscis (8) and can infect another
human when the midge takes a blood meal
(1).

Onchocerciasis

Onchocerca volvulus
Causes onchocerciasis or river blindness
which is a major cause of blindness in some
parts of Africa
Vector: black fly (Simulium)

6 of
x

[E na na, whats my name?]

Adult worms: wire-like, whitish, lie coiled

within fibrous tissue capsules
o Females: 50cm; Males: 5cm
Microfilariae: unsheathed 15-350m; often
found in the skin rarely in urine, blood, and
sputum
Developing worms wander through
subcutaneous tissues
Most worms become encapsulated nodules
are produced

During a blood meal, an infected blackfly

(Simulium) introduces 3rd stage filarial larvae
onto the skin of the human host, where they
penetrate into the bite wound (1).
In the subcutaneous tissues the larvae (2)
develop into the adult filariae, which
commonly reside in the nodules of the
subcutaneous tissue (3).
Adults can live for approximately 15 years.
Some nodules may contain numerous male
and female worms. In the subcutaneous
nodules, the female worms are capable of
producing microfilariae for approximately 9
years. (4).
A black fly ingests the microfilariae during a
blood meal (5).
After ingestion, the microfilariae migrate from
the blackflys midgut through the hemocoel to
thoracic muscles (6).
There the microfilariae develop into 1st stage
larvae (7) and subsequently into 3rd stage
infective larvae (8).
The 3rd stage infective larvae migrate to the
flys proboscis (9) and can infect another
human when the vector takes a blood meal
(1).
Clinical Manifestations
Onchocerciasis can cause pruritus, dermatitis,
onchocercoma or sowda (subcutaneous
nodules)& lymphadenopathies
The most serious manifestation consists of
ocular lesions that can progress to blindness

Blood and Tissue Nematodes

Fig. 6. Onchocercoma (L) and river blindness (R )

Review: Filariasis = Lymphatic Filariasis ,Loaisis

,Mansonelliasis ,Onchocerciasis

Generalities of Filariasis
Periodicity
Fluctuations in numbers of microfilariae
present in the peripheral blood during a 24hour period

Table 3. Periodicity of filariasis

Periodici
ty
Nocturn
ally
periodic
Diurnally
periodic
Nonperi
odic or
aperiodi
c

Subperio
dic

1.

Definition
Species found in the
blood during night time
hours but absent at
other times
Present only during
certain daytime hours
Microfilariae that
circulate in the blood
throughout a 24 hour
period without
significant changes in
their numbers
Microfilariae normally
present in the blood at
all hours but whose
density increases
significantly during
either the night or day

Example
s
W.
bancrofti
and B.
malayi
Loa loa

[E na na, whats my name?]

Mansonia
spp.

B. malayi

Diagnosis
Examination of blood samples to identify
microfilariae

7 of
x

Blood samples can be a thick smear,

stained with Giemsa or H&E

For increased sensitivity, concentration

techniques can be used :
o Centrifugation of the blood sample lyzed
in 2% formalin (Knotts technique), or
filtration through a Nucleopore
membrane

Examination of skin snips will identify

microfilariae of Onchocerca volvulus and
Mansonella streptocerca
o Skin snips are obtained using a cornealscleral punch, or a scalpel & needle
o Allow sample to incubate for 30 minutes
to 2 hours in saline or culture medium,
and then examined for microfilariae that
would have migrated from the tissue to
the liquid phase of the specimen
2. Finding of microfilariae in the blood as seen in
wet or thick blood smears taken between 8pm
and 4am

W. bancrofti microfilariae nocturnal

periodicity

B. malayi microfilariae Subperiodic

periodicity

In low intensity infection, Knotts method

for concentration may be used

DEC (Diethylcarbamazepine) provocative

test stimulates microfilariae to come out to
peripheral circulation allowing blood smear
collection even during daytime
3. Antigen detection techniques to detect
circulating filarial antigens (CFA) useful in low
and variable infection

Diagnostic Findings
Antigen detection using an immunoassay for
circulating filarial antigens useful because
microfilaremia can be low and variable
o
A rapid-format immunochromatographic
test, applicable to W. bancrofti antigens,
has been recently evaluated in the field
Molecular diagnosis using PCR is available for
W. bancrofti & B. malayi
Antibody detection has limited value
o Substantial antigenic cross reactivity
exists between filarial and other
helminths, and a positive serologic test
does not distinguish between past and
current infections
Identification of adult worms is possible from
tissue samples collected during nodulectomies
(Onchocerciasis), or during subcutaneous
biopsies or worm removal from the eye
(Loaiasis)

Blood and Tissue Nematodes

Special Procedures for Detecting Blood

Microfilariae
Capillary (fingerstick) blood
o Since microfilariae concentrate in the
peripheral capillaries, thick and thin
smears prepared from fingerstick blood
are recommended
Anticoagulated (EDTA) venous blood (1ml)
should be concentrated by one of the following
methods
o Centrifugation (Knotts technique) uses
2% formaldehyde
o Filtration uses membrane filter
(Millipore or Nucleopore membrane
filter)
Ultrasonography, contrast lymphangiography,
lymphscintigraphy
o May demonstrate live worms in the
lymphatics
Treatment
Different drugs are recommended for the
treatment of filariasis depending on the
specific causal agent
Diethylcarbamazine citrate (DEC) DRUG
OF CHOICE
o Bancroftian filariasis 6 mL/day orally
for 12 days (given in divided doses after
meals)
o Brugian filariasis 3 to 6 mg per kg per
day up to 36 to 72 mg/bw
Ivermectin 200 to 400 g/kg single oral dose
= as effective as 12 days of DEC
Prevention and Control
Goal for endemic communities: Eliminate
microfilariae in the blood to prevent
transmission of disease by vectors
Control of transmission:
o Identification of endemic areas
o Implementation of mass treatment
programs using Albendazole/DEC or
DEC/Ivermectin combination in areas
where onchocercosis or loaiasis is
prevalent
Personal protective measures
Vector control: Development of sprays and
polyester beads to seal latrines

TRICHINOSIS/TRICHENELLOSIS

Trichenella
In addition to the classical agent T. spiralis
(found worldwide in many carnivorous and
omnivorous animals), several other species of
Trichinella are now recognized:

8 of
x

[E na na, whats my name?]

o
o
o
o

T. pseudospiralis (mammals and birds

worldwide)
T. nativa (Arctic bears)
T. nelson (African predators and
scavengers)
T. britovi (carnivores of Europe and
western Asia)

Table 4. Different forms of Trichenella

Form
Female
adult

Male
adult

Larva

Description
2.2 mm in length (3.5 mm by 0.06
mm)
Single ovary in the posterior part of
the body ; Has oviduct, seminal
receptacle, coiled uterus, vagina
and vulva in the anterior 5th on the
ventral side of the body;
Viviparous females (life span: 30
days) can produce > 1500 larvae
Approximately 1.2 mm,
Single testis located near the
posterior end and is joined in the
mid-body by the genital tube,
which in turn extends back to the
cloaca;
Cloaca has a pair of caudal
appendages and 2 pairs of papillae
80 120 m by 5.6 m at birth;
Has a spear like burrowing anterior
tip;
Infective larvae are encysted in the
muscle fiber of the host this is
used as a diagnosis through biopsy
or autopsy specimens

Life Cycle
DIAGNOSTIC: encysted larvae in striated
muscle
INFECTIVE: encysted larvae

Blood and Tissue Nematodes

Figure 7. Life cycle of Trichenella

Trichinellosis is acquired by ingesting meat

containing cysts (encysted larvae) (1) of
Trichinella.
After exposure to gastric acid and pepsin, the
larvae are released (2) from the cysts and
invade the small bowel mucosa where they
develop into adult worms (3).
After 1 week, the females release larvae (4)
that migrate to the striated muscles where
they encyst (5).
Trichinella pseudospiralis, however, does not
encyst.
Encystment is completed in 4-5 weeks and the
encysted larvae may remain viable for several
years. Ingestion of the encysted larvae
perpetuates the cycle.
Rats and rodents are primarily responsible for
maintaining the endemicity of this infection.
Carnivorous/omnivorous animals, such as pigs
or bears feed on infected rodents or meat from
other animals.
Humans are accidentally infected when eating
improperly processed meat of these
carnivorous animals (or eating food
contaminated with such meat).
Clinical Manifestations
Light infections may be asymptomatic
Intestinal invasion is accompanied by GI
symptoms:
o Diarrhea, abdominal pain, vomiting

9 of
x

[E na na, whats my name?]

Larval migration into muscle tissues (one week

after infection) can cause
o Periorbital and facial edema,
conjunctivitis, fever, myalgias, splinter
hemorrhages, rashes, and blood
eosinophilia
Occasional life-threatening manifestations:
o Myocarditis, central nervous system
involvement, and pneumonitis
o Larval encystment in the muscles
causes myalgia and weakness, followed
by subsidence of symptoms.
Severity of symptoms depend on intensity of
infection
o Light infection: patients harboring up to
10 larvae
o Moderate infection: 50-500 worms
o Severe and potentially fatal: > 1,000
larvae
Full recovery expected since its a self-limiting
disease
Complications: myocardial and neurologic
Prognosis is good in mild infections
o Death is uncommon except in cases
with complications (heart failure,
encephalitis, pneumonia, sepsis)
o Low-grade or absent peripheral blood
eosinophila poor prognosis

Table 5. Phases of Clinical Conditions

Phase
Enteric

Invasio
n

Conval
escent

Description
Stage of
incubation
and intestinal
invasion
Larval
migration &
muscle
invasion

Encystment
and
encapsulation

S/Sx
Diarrhea or
constipation,
vomiting, cramps,
malaise, nausea
Myalgia, periorbital
edema &
eosinophilia
cardinal signs and
symptoms;
Also high remittent
fever, dyspnea,
dysphagia, difficulty
chewing, paralysis
of extremities, GI
hemorrhage,
splenomegaly
Abatement of fever,
pain, weakness and
other symptoms

Diagnosis
Based on Hx of exposure and PE
Most definitive diagnostic exam demonstration of larva using muscle biopsy

Blood and Tissue Nematodes

Biochemical test: elevated CPK, LDH and

myokinase
High blood count and peripheral eosinophilia
strengthen diagnosis
Serology may provide confirmatory diagnosis
Becks xenodiagnoses: when meat is
suspected on harboring encysted larva
o Feeding the meat to albino rats; observe
them 14 days after for female worm in
the duodenum and larvae in the
muscles of experimental host
Suspicion of trichinellosis (trichinosis) based
on clinical symptoms and eosinophilia
Can be confirmed by specific diagnostic tests:
antibody detection, muscle biopsy and
microscopy
Treatment
Should begin as soon as possible
Bed rest, supportive treatment

Table 6. Treatment for Trichinella infection

Drug
Thiabenda
zole

Mebendaz
ole
Albendazo
le
Steroids

Description
25 mg/kg 2x/d for 7d
Expels adult worm from GIT
during 1st week of infection;
Has no effect on migrating
larvae and is useless for
infections detected two weeks
after exposure
Larvicidal when given at
20mg/kg every 6hrs for 10-14
days
Shows promise but has not yet
been sufficiently evaluated
Used for infections with severe
symptoms;
Prednisone 20mg 3x daily
tapered over 2-3 weeks

Epidemiology
Occurs whenever meat is part of the diet
Humans get infected after ingestion of raw or
insufficiently cooked meat of infected animals.
Infection is maintained in a pig-to-pig or pigto-rat-to-pig cycle
Prevention and Control

Health education

Smoking, salting, drying not effective

Cook meat 77C

Freezing at -15C for 20 days or -30C for six
days can kill the larvae

10 of
x

[E na na, whats my name?]

Meat inspection and keeping pigs in rat-free

pens

ANGIOSTRONGYLIASIS
Causal agents:

Angiostrongylus cantonensis (rat

lungworm) = Human Eosinophilic Meningitis

Angiostrongylus (Parastrongylus)
costaricensis = Abdominal or Intestinal
Angiostrongyliasis
Angiostrongylus cantonensis
Form
Description
Female
21-25 mm by 0.30 -0.36 mm;
adult
Has uterine tubules which are
wound spirally around the
intestine;
BARBERS POLE pattern;
Lays up to 15000 eggs/day
Male
16 19 mm by 0.26 mm;
adult
Well-developed caudal bursa which
is kidney shaped and single lobed
Life Cycle
INFECTIVE to intermediate host: 1st stage larvae
INTERMEDIATE HOST: Snails or slugs
INFECTIVE to definitive host: 3rd stage larvae
DEFINITIVE HOST: Rats and rodents
INCIDENTAL HOSTS: Humans

Blood and Tissue Nematodes

Figure 8. Life cycle of Angiostrongylus cantonensis

Adult worms of A. cantonensis live in the

pulmonary arteries of rats
The females lay eggs that hatch, yielding 1st
stage larvae, in the terminal branches of the
pulmonary arteries.
The 1st stage larvae migrate to the pharynx,
are swallowed, and passed in the feces.
They penetrate, or are ingested by, an
intermediate host (snail or slug).
After two molts, 3rd stage larvae are
produced, which are infective to mammalian
hosts.
When the mollusk is ingested by the definitive
host, the 3rd stage larvae migrate to the brain
where they develop into young adults.
The young adults return to the venous system
and then the pulmonary arteries where they
become sexually mature.

Known intermediate hosts in the Philippines:

o Slugs and snails
o Achatina fulica
o Hemiplecta sagittifera
o Helicostyla macrostoma
o Vaginilus plebeius
o Veronicella altae
o The African Giant Snail

Many animals act as paratenic (transport)

hosts: after ingesting the infected snails, they
carry the 3rd stage larvae which can resume
their development when the paratenic host is
ingested by a definitive host.
Humans acquire the infection by eating raw
or undercooked snails or slugs, vegetables
contaminated with mollusks secretions, or
infected paratenic animals (crabs, freshwater
shrimps)
o Development of the 3rd stage larvae is
stalled in the brain, where they die
In humans, juvenile worms migrate to the
brain, or rarely in the lungs, where the worms
ultimately die
The life cycle of Angiostrongylus
(Parastrongylus) costaricensis is similar,
except that the adult worms reside in the
arterioles of the ileocecal area of the definitive
host
In humans, A. costaricensis often reaches
sexual maturity and release eggs into the
intestinal tissues. The eggs and larvae
degenerate and cause intense local
inflammatory reactions and do not appear to
be shed in the stool

11 of
x

[E na na, whats my name?]

Clinical Manifestations
Incubation period is usually between 6-15 days
Intermittent occipital or bitemporal headache
is often the chief complaint
Eye involvement: hemorrhage & retinal
detachment
Clinical symptoms of eosinophilic meningitis
are caused by the presence of larvae in the
brain and by local host reactions
o Severe headaches, nausea, vomiting,
neck stiffness, seizures, and neurologic
abnormalities may occur
Occasionally, ocular invasion may be present
Eosinophilia is observed in most of cases
Most patients recover fully
Abdominal angiostrongyliasis mimics
appendicitis, with eosinophilia
Diagnosis
In eosinophilic meningitis the cerebrospinal
fluid (CSF) is abnormal (elevated pressure,
proteins, and leukocytes; eosinophilia).
On rare occasions, larvae have been found in
the CSF.
CT scans may show meningeal lesions
Serologic confirmation - ELISA
In abdominal angiostrongyliasis, eggs and
larvae can be identified in the tissues removed
at surgery
Presumptive diagnosis is made by travel and
exposure history
In humans, eggs and larva are not normally
excreted but remain sequestered in tissues.
Both eggs and larvae (occasionally adult
worms) of A. costaricensis can be identified in
biopsy or surgical specimens of intestinal
tissues. The larvae need to be distinguished
from larvae of Strongyloides stercoralis,
however, the presence of granulomas
containing thin shelled eggs and/or larvae
serve to distinguish A. costaricensis infections.
Treatment
No antihelminthic treatment is recommended
at present although mebendazole,
thiabendazole albendazole and ivermectin
were found to be successful in animal
experiments
Antihelminthics are usually not necessary
because the disease is self-limiting and killing
the worms may bring about greater
inflammatory reactions
Analgesics; removal of spinal fluid at regular
intervals can relieve headache

Blood and Tissue Nematodes

Prednisone 30mg daily: recommended in

severe cases with cranial nerve involvement
Surgical removal: when parasite is lodged in
the anterior chamber of the eye
Prognosis is usually good
Infection is self-limiting, complete recovery
usually occurs
Permanent neurologic deficits do occur and
may occasionally be fatal

DEFINITIVE HOSTS: Dogs

ACCIDENTAL HOSTS: Humans

TOXOCARIASIS

Toxocara canis
Toxocariasis is caused by the larvae of
Toxocara canis (dog roundworm) and less
frequently of T. cati (cat roundworm)
Accomplishes its life cycle in dogs, with
humans acquiring the infection as accidental
hosts
Puppies are infected with T. canis as early as
the fetal stage or at birth due to transplacental
and transmammary transmission (important
source of eggs)
Man becomes infected by ingestion of
embryonated eggs through contaminated food
and water
Other mammals and birds may serve as
paratenic hosts
This disease occurs worldwide
Parasite Biology
Males, 4-6 cm long, are smaller than females.
The male's posterior end is curved ventrally
and the tail is bluntly pointed.
The female worms are generally around 6.5
cm but can be as long as 15 cm long.
Egg contains a well-developed larvae ; this will
be infective if ingested by a human
(frequently, a child).
These eggs are passed in dog feces, especially
in puppies
Human infections do not produce or excrete
eggs, and therefore eggs are not a diagnostic
finding in human toxocariasis

Fig. 10. Life cycle of Toxocara canis

Fig. 9. Toxocara canis larva hatching

Life Cycle
INFECTIVE : Embryonated eggs with larvae

12 of
x

[E na na, whats my name?]

T. canis accomplishes its life cycle in dogs,

with humans acquiring the infection as
accidental hosts. Unembryonated eggs are
shed in the feces of the definitive host (1).
Eggs embryonate and become infective in the
environment (2).
Following ingestion by dogs (3), the infective
eggs hatch and larvae penetrate the gut wall.
In younger dogs, the larvae migrate through
the lungs, bronchial tree, and esophagus;
adult worms develop and oviposit in the small
intestine (4).

In older dogs, patent infections can also occur,

but larval encystment in tissues is more
common. Encysted stages are reactivated in
female dogs during late pregnancy and infect
by the transplacental and transmammary
routes the puppies (5), in whose small
intestine adult worms become established (6).
Puppies are a major source of environmental
egg contamination. Toxocara canis can also be
transmitted through ingestion of paratenic
hosts: eggs ingested by small mammals
(rabbits) hatch and larvae penetrate the gut

Blood and Tissue Nematodes

wall and migrate into various tissues where

they encyst (7).
The life cycle is completed when dogs eat
these hosts (8) and the larvae develop into
egg-laying adult worms in the small intestine.
Humans are accidental hosts who become
infected by ingesting infective eggs in
contaminated soil (9) or infected paratenic
hosts (10).
After ingestion, the eggs hatch and larvae
penetrate the intestinal wall and are carried by
the circulation to a wide variety of tissues
(liver, lungs, brain, muscle, eyes) (11).
While the larvae do not undergo any further
development in these sites, they can cause
severe local reactions that are the basis or
Toxocarasis.
Clinical Manifestations
Many human infections are asymptomatic,
with only eosinophilia and positive serology as
the only indications of infection
Death can occur rarely, by severe cardiac,
pulmonary, or neurologic involvement

Table 7. Two main clinical manifestations

Disease
Viscera
l larva
migran
s (VLM)

Ocular
larva
migran
s (OLM)

Description
Larvae invade
multiple tissues
(liver, heart,
lungs, brain,
muscle) and cause
various symptoms

Larvae produce
various
ophthalmologic
lesions, which in
some cases have
been
misdiagnosed as
retinoblastoma,
resulting in
surgical
enucleation

S/Sx
Fever, anorexia,
weight loss,
cough,
wheezing,
rashes,
hepatosplenom
egalyand
hypereosinophil
ia ; Occurs
mostly in
preschool
children
Often occurs in
older children
or young
adults, with
only rare
eosinophilia or
visceral
manifestations

Diagnosis
Diagnosis does not rest on identification of the
parasite

13 of
x

[E na na, whats my name?]

Since the larvae do not develop into adults in

humans, a stool examination would not detect
any Toxocara eggs
o Presence of Ascaris and Trichiuris eggs
in feces, indicating fecal exposure,
increases the probability of Toxocara in
the tissues
For both VLM and OLM, a presumptive
diagnosis rests on clinical signs, history of
exposure to puppies, laboratory findings
(including eosinophilia), and the detection of
antibodies to Toxocara
Antibody Detection: The only means of
confirmation of a clinical diagnosis of visceral
larva migrans (VLM), ocular larva migrans
(OLM), and covert toxocariasis (CT),
o
The currently recommended serologic
test for toxocariasis is enzyme
immunoassay (EIA)
Toxocara excretory-secretory (TES) antigens
are preferable to larval extracts because they
are convenient to produce and because an
absorption-purification step is not required for
obtaining maximum specificity
Treatment
VLM: treated with antiparasitic drugs, usually
in combination with anti-inflammatory
medications
OLM: more difficult to treat and usually
consists of measures to prevent progressive
damage to the eye.
o
Albendazole, Mebendazole

ANISAKIASIS

Anisakis
Caused by the accidental ingestion of the larve
of Anisakis simplex and Pseudoterranova
decipiens
Larval stages of anisakine nematodes persist
in the alimentary canal or penetrating the
tissues of humans after consuming raw or
semi-raw fish, as in sushi
Fish species acts as intermediate/transport
hosts for the larva
Larva matures into adults in warm-blooded
marine mammals
No human case yet reported in the Philippines
but the potential for infection is great
Parasite Biology
Has a pseudocoel
Complete digestive system
Cuticle has 3 main layers and shed 4 times
during their life cycle

Blood and Tissue Nematodes

Length: 5-30 mm
Sexual dimorphism: females are larger
Life Cycle

Fig. 11. Life cycle of Anisakis simplex

Adult stages of Anisakis simplex or

Pseudoterranova decipiens reside in the
stomach of marine mammals, where they are
embedded in the mucosa, in clusters.
Unembryonated eggs produced by adult
females are passed in the feces of marine
mammals .
The eggs become embryonated in water, and
first-stage larvae are formed in the eggs.
The larvae molt, becoming second-stage
larvae , and after the larvae hatch from the
eggs, they become free-swimming .
Larvae released from the eggs are ingested by
crustaceans . The ingested larvae develop into
third-stage larvae that are infective to fish and
squid .
The larvae migrate from the intestine to the
tissues in the peritoneal cavity and grow up to
3 cm in length.
Upon the host's death, larvae migrate to the
muscle tissues, and through predation, the
larvae are transferred from fish to fish.
Fish and squid maintain third-stage larvae that
are infective to humans and marine
mammals . When fish or squid containing

14 of
x

[E na na, whats my name?]

third-stage larvae are ingested by marine

mammals, the larvae molt twice and develop
into adult worms.
The adult females produce eggs that are shed
by marine mammals . Humans become
infected by eating raw or undercooked
infected marine fish
After ingestion, the anisakid larvae penetrate
the gastric and intestinal mucosa, causing the
symptoms of anisakiasis.
Clinical Manifestations
Within hours after ingestion of infected larvae,
violent abdominal pain, nausea, and vomiting
may occur.
Occasionally the larvae are coughed up
If the larvae pass into the bowel, a severe
eosinophilic granulomatous response may also
occur 1 to 2 weeks following infection, causing
symptoms mimicking Crohn's disease
Diagnosis
Diagnosis can be made by gastroscopic
examination during which the 2 cm larvae are
visualized and removed
Histopathologic examination of tissue removed
at biopsy or during surgery
Treatment, Prevention & Control
The treatment of choice is surgical or
endoscopic removal
Avoid ingestion of raw or undercooked seafood

Fig. 12. Fish with Anasakis

Epidemiology
Found worldwide, with higher incidence in
areas where raw fish is eaten (e.g., Japan,
Pacific coast of South America, the
Netherlands).
Increasing incidence in the US due to
increased consumption or raw fish.

MORE MORE MORE

Appendix A. Comparison of microfilariae sizes and
morphology from Dr. Nacpils ppt

Blood and Tissue Nematodes

Species
W. bancrofti

Morphology
Sheathed, Tail pointed and clear

B. malayi

Sheathed, Tail pointed with 2 nuclei

L. loa
M. ozzardi
M. perstans

Geographi
cal
distributio
n
Vectors

Microfilariae size
210- 320 m
By 8-10 m
170-260 m
By 5-6 m
230 300 m
By 6-8 m
250 m by 6-7 m
200 m by 6 m
W. bancrofti
B. malayi
B. timori

Tropics and
subtropics
worldwide

South East Asia;

Indian
subcontinent

Mosquitoes:
Culex, Aedes,
Anopheles,
Mansonia
Lymphatic
system

Mosquitoes:
Aedes,
Anopheles,
Mansonia
Lymphatic
system

Microfilari
ae habitat

Blood

Periodicity

Sheathed, Tail blunt with nuclei

Unsheathed, Tail pointed and clear
Unsheathed, Tail blunt with nuclei
L. loa
M. ozzardi

M. perstans

Indonesian
archipelago,
Timor, Lesser
Sunda
Mosquitoes:
Anopheles

West and
Central Africa

Caribbean,
Central and
South America

Africa and
South America

Tabanid flies;
deer flies
(Chrysops)

Biting midges
(Culicoides)

Lymphatic
system

Subcutaneous
tissue,
conjunctiva

Biting midges
(Culicoides),
black flies
(Simulium)
Subcutaneous
tissue

Blood

Blood

Blood

Blood

Mesenteries,
connective
tissue of
abdominal
organs
Blood

Nocturnal

Nocturnal

Nocturnal

Diurnal

Aperiodic

Aperiodic

Sheath

Present

Present

Present

Present

Absent

Absent

Width
(m)

7.5-10

5.0-6.0

4.5-6.0

5.0-7.0

3.0-5.0

4.0-5.0

Tail

Tapered,
anucleate

Tapered;
nuclei
irregularly
spaced to end
of tail
Single row of
nuclei to end
of tail, sheath
unstained in
Giemsa

Bluntly
rounded nuclei
to end of tail

Short head
space,
dispersed
nuclei, sheath
unstained in
Giemsa, body
in smooth
curves

Tapered;
subterminal and
terminal nuclei
widely
separated
Long head
space, sheath
unstained in
Giemsa,
terminal and
subterminal
nuclei

Long, slender,
pointed,
anucleated

Key
features
of
microfilari
ae

Tapered;
subterminal and
terminal nuclei
widely
separated
Long head
space, sheath
stains in
Giemsa,
terminal and
subterminal
nuclei

Small size,
long slender
tail, aperiodic

Small size,
blunt tail filled
nuclei,
aperiodic

Adult
habitat

Summary from Dra. Nacpils ppt

15 of
x

[E na na, whats my name?]