MLS 108 LECTURE | BLOOD AND TISSUE NEMATODES

THE FILARIAE

LYMPHATIC FILARIASIS
• Considered globally as a Neglected Tropical
Disease
• Lymphatic Filariasis (LF) is one of the most
debilitating diseases plaguing many tropical
countries
• Disease is transmitted by blood-feeding
arthropod vectors, mainly mosquitoes and
black flies (arthropod-borne infections) IDENTIFYING CHARACTERISTICS
• The microfilariae are sheathed
FILARIAL NEMATODES • The tail is pointed, and there are no nuclei in
1. Subcutaneous the tip.
• Loa loa (African eye worm) • The cephalic space is not as long as it is wide,
• Onchocerca volvulus and the nuclei in the nuclear column are
• Mansonella streptocerca distinct.
2. Serous cavity
• Mansonella – serous cavity in
abdomen
3. Lymphatic Filariasis
• Wuchereria bancrofti
• Brugia malayi
• Brugia timori Adult:
WUCHERERIA BANCROFTI • creamy white, long, and filiform in shape
• bancroftian filariasis (most common filarial • male : 20 – 40 mm length
species to infect humans) • female : 80 – 100 mm
• Adult worms - lymphatic system>
lymphadenopathy and lymphangitis,
>lymphedema and obstructive fibrosis
• Severe involvement of the lower extremities
and genitalia may result in elephantiasis.

• In most areas, microfilariae circulate in

peripheral blood with a nocturnal
periodicity that corresponds with the
W. BANCROFTI MICROFILARIAE: feeding activities of the usual vectors:
TYPICAL CHARACTERISTICS • a. Culex (quinquefasciatus)
• b. Aedes (polynesiensis)
PARAMETER DESCRIPTION • c. Anopheles
Size Range 240-300 long • d. Mansonia
Sheath Present • e. Coquillettidia
Arrangement of nuclei Tip of tail free of nuceli
in tail
 MLS 108 LECTURE | BLOOD AND TISSUE NEMATODES

• Microfilariae migrate from the parent worm,

through the walls of the lymphatics, and into
the neighboring blood vessels.
W. BANCROFTI: PATHOGENESIS

LYMPHANGIECTASIA
- Common features
- Parasite-induced lymphatic dilation cause by
adult filarial worms
LYMPHANGIOGENESIS
- Lymphatic endothelial cell proliferation and
differentiation leading to collateralization
- Induced by live filarial parasites or filarial Ag
CHRONIC LF
- Fibrosis and cellular hyperplasia in and around
the lymphatic walls
- Contributes to edema and collagen
accumulation
- Dead and decalcifying worms causes
lymphatic blockage
• Gross pathological lesions: pain and
swelling
• Exposure to Wolbachia released by
dying worms induces inflammation
CLINICAL SPECTRUM OF LF
a. asymptomatic microfilaremia
b. Acute dermatolymphangiodenitis (ADLA)
Previously called adenolymphangitis (ADL)
c. Acute filarial lymphangitis (AFL)
d. Lymphedema and elephantiasis
IN THE MOSQUITO
• Microfilariae ingested by the mosquito migrates e. Genitourinary lesions (hydrocele)
to its muscles where they develop into first (L1) f. Tropical pulmonary eosinophila (TPE)
second (L2), and third (L3) stage larvae. ASYMPTOMATIC FILARIASIS
• After 6-20 days of development, 3rd stage - Adults exhibit microfilariae in their blood
larvae force they way out of the muscles, without experiencing symptoms; Eosinophilia
causing considerable damage, and migrate - Moderate generalized enlargement of lymph
towards the mosquito’s head and proboscis. nodes, esp. in the inguinal region
• During a blood meal, larvae emerge from the - Expatriate Syndrome - characterized by clinical
proboscis onto the skin of the susceptible host. and immunologic hyper-responsiveness to the
IN HUMANS mature or maturing worms
• Larvae penetrate the skin and reach the ACUTE DERMATOLYMPHAGIOADENITIES
lymphatic vessels and nodes where they (ADLA)
develop into adult worms. - localized pain, lymphadenitis and/or
• They are usually localized in the lymph vessels lymphangitis and/or cellulitis and local warmth,
of the lower extremities, inguinal lymph nodes, with or without systemic manifestations of
epididymis of males, and labia of females. fever, nausea, and vomiting
- Group A streptococcus – bacteria frequently
associated with ADLA
 MLS 108 LECTURE | BLOOD AND TISSUE NEMATODES

- repeated ADLA episodes are responsible for STAGE 1:

lymphedema progression and elephantiasis - Swelling reverses at night
- most common acute manifestation of LF, with - Skin folds-absent
recurrent attacks - Skin: Smooth, Normal
- Clinical description similar to erysipelas and
cellulitis

STAGE 2:
- Swelling not reversible at night
- Skin folds-absent
- Skin: Smooth, Normal
AFL (ACUTE FILARIAL LYMPHANGITIS
- rare manifestations caused by adult worms that
died spontaneously or after treatment with DEC
- Characterized by lymphangitis that progresses
distally along lymphatic vessel, producing a
palpable “cord”
LYMPHEDEMA AND ELEPHANTIASIS STAGE 3:
- most common chronic manifestation - Swelling not reversible at night
- lower limbs commonly affected - Skin folds-shallow
- upper limbs and genitalia may be involved - Skin: Smooth, Normal
- females: breast and genitalia

STAGE 4:
- Swelling not reversible at night
- Skin folds-shallow
- Skin: Irregular, Knobs, Nodules
STAGES OF CHRONIC LYMPHEDEMA

STAGE 5:
- Swelling not reversible at night
- Skin folds-deep
- Skin: Smooth, Irregular
 MLS 108 LECTURE | BLOOD AND TISSUE NEMATODES

STAGE 6: INFLAMMATORY FILARIASIS

- Swelling not reversible - immunologic phenomenon caused by
- Mossy lesions sensitization to the products of the living and
- Wart-like lesions on foot or top of the toes dead adult worms.
- Recurrent attacks are characterized by
funiculitis, epididymitis, orchitis and localized
areas of swelling and redness of the arms and
legs.

STAGE 7:
- Swelling not reversible at night
- Skin folds-deep
- Needs help for daily activity
• Waling, bathing, using bathrooms, IN MALES:
dependent on family or health care - acute lymphangitis of spermatic cord,
systems epididymitis, orchitis, and scrotal edema.

TROPICAL PULMONARY EOSINOPHILIA (TPE)

- a classic example of occult Filariasis
- Microfilaria not found in the blood but may be
found in the tissues
- The syndrome is brought about by the
immunologic hyper - responsiveness to filarial ACUTE GRANULOMATOUS REACTION
infection (LYMPHATICS)
- Characterized by paroxysmal nocturnal cough - resulting from the worms and their toxic
- Hypereosinophilia (3,000 – 5,000 cells per products (manifest by local inflammation and
mm3 of blood) systemic symptoms) gradually merges into a
- In most cases, lung function is impaired chronic proliferative overgrowth of fibrous
W. BANCROFTI : PATHOGENESIS tissue around the dead worms, produces
HYDROCELE OR CHYLOCELE lymphatic obstruction, recurrent attacks of
lymphangitis, and elephantiasis.
 MLS 108 LECTURE | BLOOD AND TISSUE NEMATODES

OBSTRUCTIVE FILARIASIS
- Elephantiasis- dramatic end result of filariasis
- O.F. develops slowly, usually follows years of
continuous filarial infection, and is preceded by
chronic edema and often by repeated acute
inflammatory attacks.
- In chronic stage the cellular reaction and
edema are replaced by fibroblastic hyperplasia
- since mcf disappear after the death of the
worms, mcf is generally absent in patients with BRUGIA MALAYI
- Malayan filaria
elephantiasis
- This species produces disease similar to that
of W. bancrofti, although it is often milder and
more frequently involves the lymphatics of the
upper extremities.

- Rupture of the lymphatics of the kidney may

produce chyluria

LABORATORY DIAGNOSIS THE PARASITE OCCURS MAINLY IN:

- Examination of fresh Giemsa-stained blood for a. India
W. bancrofti microfilariae – diagnostic method b. South-east Asia
of choice c. Korea
d. Philippines
- Knott technique
e. Japan
- Serologic tests (antigen and antibody f. The microfilariae circulate in the blood and are
detection and PCR assays) primarily periodic.
TREATMENT g. Microfilarial sheaths of Brugia malayi stain
- diethylcarbamazine (DEC) and ivermectin well with Giemsa stain.
(Stromectol) when used in combination with
albendazole
- DEC and ivermectin kill microfilariae
- Increased doses are necessary to kill adults
- Surgical removal of excess tissue may be
appropriate for the scrotum but is only rarely
successful when performed on the extremities
- The use of special boots, known as Unna’s - The tail has a swelling at the tip and has two
paste boots, as well as elastic bandages and solitary nuclei located beyond the end of the
simple elevation, have proven successful in nuclear column (termed subterminal and
reducing the size of an infected enlarged limb. terminal nuclei).
- The cephalic space may be much longer than
PREVENTION AND CONTROL
it is wide.
 MLS 108 LECTURE | BLOOD AND TISSUE NEMATODES

B. MALAYI MICROFILARIA: TYPICAL BRUGIA TIMORI

CHARACTERISTICS AT A GLANCE - Brugia timori is a distinct species occurring in
the eastern end of the Indonesian archipelago
PARAMETER DESCRIPTION (islands of Timor and Flores)
Size Range 200-280 um long
- Microfilariae are very similar to those of B.
Sheath Present
Arrangement of nuclei in Presence of two distinct malayi, although somewhat larger.
tail nuclei in the tip of the - Female – 43 to 55 mm in length by 130 to 170
tail; the organism tissue μm in width,
tends to bulge around - Males – 13 to 23 mm in length by 70 to 80 μm
each of the two nuclei in width.
- Microfilariae – 177 to 230 μm in length and 5
ADULT
to 7 μm in width
- creamy white, long, and filiform in shape
- sheathed
- male: 13 – 23 mm length
- nocturnal periodicity
- female: 43 – 55 mm
- Vector – Mansonia and Aedes

LOA LOA
- Eye worm
- Lives in subcutaneous tissues
- The nematodes migrate continuously,
producing transient (2-3 days) local
PREVENTION AND CONTROL inflammatory reactions known as Calabar or
fugitive swellings.
- Their occasional appearance in the conjunctiva
allows them to be surgically excised.

LOA LOA MICROFILARIA: TYPICAL

CHARACTERISTICS AT A GLANCE

PARAMETER DESCRIPTION
Size Range 248-300 µm long
Sheath Present
Arrangement of nuclei in Distinct continuous row
tail of nuclei; extend to tip of
tail
 MLS 108 LECTURE | BLOOD AND TISSUE NEMATODES

ADULT
- white, cylindrical threadlike appearance
- male: 28 to 35 mm length
- female: 38 to 72 mm
- Loiasis occurs primarily in west and central
Africa, where deer flies of the genus Chrysops
serve as vector LABORATORY DIAGNOSIS
Other vectors: - Examination of fresh Giemsa-stained blood for
• Horse flies (Tabanidae) L. loa microfilariae – diagnostic method of
• Mango flies choice (diurnal periodicity: 10:15 AM and 2:15
- The microfilariae, which circulate in the blood PM)
with diurnal periodicity, are sheathed (does - migrating adult worms (extracted eye)
not stain with Giemsa's stain) - Knott technique
- Nuclei in the tail extend to the rounded tip. - Serologic tests
- The nuclear column is distinct, and the EPIDEMIOLOGY
cephalic space is short. - Africa especially the rainforest belt region
- 70 % in the areas in which a large vector
population exists
- Less than 10 % infection rate in regions in
which minimal numbers of vectors reside
TREATMENT
- Surgical removal of adult Loa loa worms is the
treatment of choice
CLINICAL SYMPTOMS - Diethylcarbamazine (DEC) – medication of
LOIASIS: choice
- After the initial bite, pruritus or itchiness and PREVENTION AND CONTROL
localized pain - Personal protection measures are essential to
- Development of Calabar swellings at the site stop the spread of Loa loa
- The adult worms may only be noticeable when - Destroying the vector breeding area
seen migrating under the conjunctiva of the - Prophylactic DEC for non- natives visiting the
eye or crossing under the skin of the bridge of endemic areas
the nose. ONCHOCERCA VOLVULUS
- Blinding filaria
- Onchocerciasis is a leading cause of
blindness in endemic areas, which include
central Africa, Central America (Mexico and
Guatemala), and northern South America.
- Vectors are black flies of the genus Simulium
 MLS 108 LECTURE | BLOOD AND TISSUE NEMATODES

- Severe allergic reactions to the presence of the

microfilariae
- Scratching leads to secondary bacterial
infections
- Onchocerciasis: River Blindness
- Blindness - when the eye becomes involved,
lesions, due to the body’s reaction to the
microfilariae
- Changes in overall skin appearance, such as
loss of elasticity, and location of nodules on the
body vary

ONCHOCERCA VOLVULUS MICROFILARIA:

TYPICAL CHARACTERISTICS AT A GLANCE

PARAMETER DESCRIPTION
Size Range 150-355 um long
Sheath Absent
Arrangement of nuclei in Do not extend to tip of
tail tail

- Adult worms live in hard, fibrous nodules in

subcutaneous and deeper tissues that can
grow to be 40 mm in diameter.
- Microfilariae in stained preparations lack both - Adult worms produce microfilariae that migrate
a sheath and nuclei in the tail tip. continuously through the skin.
- Complications arise from the migratory
activities of the microfilariae, resulting in
several forms of dermatitis.
- Movement of microfilariae through the surface
of the eye may result in keratitis, corneal
opacity, and damage to the anterior and
posterior chambers and iris, thus leading to
blindness with repeated infections over time.
ADULT
- thin and wirelike in appearance; coil up in knots
inside infected skin nodules
- mal: 25 to 50 mm length
- female: up to 500 mm
CLINICAL SYMPTOMS
- Onchocerciasis: River Blindness
- Chronic and nonfatal condition
- Patients typically experience localized
symptoms caused by the development of
infected nodules
 MLS 108 LECTURE | BLOOD AND TISSUE NEMATODES

LIFE CYCLE NOTES MANSONELLA SPP.

- On entrance into the human host a following - Several species of Mansonella infect humans,
maturation, the resulting adult worms but all are generally regarded as causing little
encapsulate in subcutaneous fibrous tumors pathology.
- The adults become coiled, and microfilariae • M. ozzardi
emerge • M. perstans
- Microfilariae may migrate throughout infected • M. streptocerca
nodules, subcutaneous tissues and skin and - (Microfilariae must be differentiated from the
into the eyes truly pathogenic filarial species)
LABORATORY DIAGNOSIS
- Multiple Giemsa-stained slides of tissue
biopsies (skin snips), collected from suspected
infected areas – specimens of choice for the
recovery of microfilariae
- The skin snips should be obtained with as little
blood as possible
- Adult worms may be recovered from infected M. OZZARDI
nodules New World filaria
- Organisms residing in the eye are best seen by - Mansonelliasis ozzardi, Ozzard’s filariasis
ophthalmologic examination using a slit lamp - found in Central and South America, and
- Serologic methods some areas of the Caribbean.
- PCR – detect low level infections - Infections are often assymptomatic but may
TREATMENT produce lympadenitis, urticaria, and
- Ivermectin – drug of choice arthralgias.
- Therapy may be necessary for very long - Mcf is present in blood and in the dermis (no
periods of time due to the long life of the adult cutaneous pathology)
worms (15 years or more) mcf periodicity tail
- Surgical removal of the adult worms from an M. ozzardi unsheathed none Thin, pointed &
infected nodule, to reduce the number of without nuclei
microfilariae present in the subcutaneous M. perstans unsheathed none broad and blunt
tissue. with nuclei
PREVENTION AND CONTROL extending to the
- Personal protection when entering the endemic tip
area
- Controlling the vector breeding grounds with M. OZZARDI & M. PERSTANS MICROFILARIA:
the use of insecticides TYPICAL CHARACTERISTICS AT A GLANCE
 MLS 108 LECTURE | BLOOD AND TISSUE NEMATODES

PARAMETER M. ozzardi M. perstans Prevention & Control

Size Range 200 µm in length about 200 µm in • Controlling the sucking midge and Simulium
length populations
Sheath Absent Absent MANSONELLA PERSTANS
Arrangement of Numerous; do Numerous; - Perstans filariasis
nuclei in tail not extend to tip extend to tip of - human is the chief definitive host
of tail tail - Intermediate host-blood sucking midges of the
genus Culicoides

ADULT

CLINICAL SYMPTOMS
- Minor allergy, Calabar swelling, lymphatic
varices, moderate eosinophilia.
- Dx: finding of nonperiodic, unsheathed mcf in
CLINICAL SYMPTOMS the blood.
- Asymptomatic infections
- Urticaria, lymphadenitis, skin itching, and
arthralgias
- Eosinophilia is common
- Adult worms cause minimal damage to the
areas they inhabit

LIFE CYCLE NOTES

- Transferred by the infective larvae to the
human definitive host
Transmission is carried out by the Culicoides
sucking midge or Simulium blackfly (M.
ozzardi)
LABORATORY DIAGNOSIS
- The microfilariae are found in the blood as well
- microfilariae may be recovered in peripheral
as in the capillaries and intravascular spaces of
blood
the skin
- no known optimum time for collecting the blood
- Adults may take up residence in the body
sample
cavities, visceral fats and mesenteries.
- Giemsa-stained microscopic examination is
TREATMENT
necessary to identify the characteristic
- Diethylcarbamazine (DEC) – treatment of
microfilariae.
choice
TREATMENT, PREVENTION, AND CONTROL
- Mebendazole
Treatment
Prevention and Control
• Ivermectin
- Use of insecticides targeted against the vector
• Diethylcarbamazine (DEC)
- Personal protection to prevent insect bites
 MLS 108 LECTURE | BLOOD AND TISSUE NEMATODES

EPIDEMIOLOGY FILARIAL INFECTIONS OF ANIMALS THAT MAY

INFECT HUMANS
M. ozzardi - Dirofilaria immitis - dogs
• Found in North, Central and South Americas - Dirofilaria tenuis – racoons
• Western Indies and Caribbean - D. repens – dogs
• Specific countries: Colombia, Peru, Haiti, - D. ursi – bears
Dominican Republic, Puerto Rico
M. perstans
• Africa
• Selected areas in the Caribbean Islands,
Panama, northern south America
M. STREPTOCERCA
- found in tropical Africa
- The unsheathed mcf found in the skin of
humans and chimpanzees have the
appearance of a walking stick with a crooked
handle (with nuclei extending to the tip).
- IH – Culicoides
- Non-pathogenic but it may cause cutaneous
edema and elephantiasis
- Infected persons are symptomless
- Diethylcarbamazine, at a dose of 150mg per
day will kill adult worms as manifested by
formation of skin papules within 3-5 days of
therapy.
- Females: 27 mm in length, diameter is 50 µm
at the level of the vulva (anteriorly) and ovaries
(near the posterior end), and up to 85 µm at the
mid-body.
- Males: 50 µm in diameter.
- Microfilarie: unsheathed and non-periodic,
measuring 180 to 240 µm by 3 to 5 µm