Lesson 3 - Filarial Nematodes (Transes)
Lesson 3 - Filarial Nematodes (Transes)
LECTURE / LESSON 3
FILARIAL NEMATODES
Filariae (1) Nocturnal (occurring at night)
Commonly known as the “filarial nematodes” (2) Diurnal (occurring during the day)
Adult worms live in tissue or the lymphatic system and are (3) Subperiodic (timing of occurrences not clear-cut)
thus rarely seen The primary method of filarial diagnosis is microscopic
The adult filariae produce larvae called microfilariae that examination of the microfilariae:
are usually detected in the blood Giemsa-stained smear of blood
Vectors of filarial nematodes include biting insects such as Tissue scraping of an infected nodule
mosquitoes Whole blood samples
Distribution of these organisms includes Asia, Africa, Processing of these samples consists of lysing the cells
South and Central Americas, and the Caribbean followed by concentrating and examining the sample for
Characteristics microfilariae using the Knott technique
1. There are two known morphologic forms of the filariae: Pathogenesis and Clinical Symptoms
adult worms and larvae (microfilariae). The clinical symptoms experienced by persons infected with
2. Adults usually appear creamy white and assume a filarial organisms vary, depending on the species.
threadlike appearance. Adult males may measure from 20 to Such symptoms range from involvement of the lymphatics:
500 mm in length, which is often half that of typical adult - Subsequent granulomatous lesions
females. - Eosinophilia
3. Microfilariae are slender and may range in size from just - Fever
under 150 µm to 350 µm in length. - Chills
4. The distribution of nuclei within the tip of the tail, as well - Enlargement of skin and subcutaneous tissue known as
as the presence or absence of a delicate transparent covering elephantiasis, to Calabar swellings (transient swelling of
known as a sheath, are the two key characteristics helpful in subcutaneous tissues)
speciating the microfilariae forms of these organisms. - Eye involvement
Life Cycle - Blindness
Adult Worms → Microfilariae → Larvae Nematode Classification
Only one to four infective larvae, injected by an infected
arthropod at the feeding site, are required to initiate human
infection.
Once inside the body, the larvae migrate to the tissues,
where they complete their development, a process that
may take up to 1 year.
The resulting adult worms may reside in the lymphatics,
subcutaneous tissue or internal body cavities.
Fertilized adult female worms lay live microfilariae, which
Wuchereria Bancrofti
take up residence in the blood or dermis. The microfilariae (wooch-ur-eer'ee-uh/ban-krof'tye)
exit the body via a blood meal by the appropriate Common name: Bancroft's Filaria
arthropod vector. Common associated disease and condition names:
The arthropod serves as the intermediate host for the
Bancroft's Filariasis or Elephantiasis
parasite. Larvae development into the infective stage takes
Epidemiology
place in the insect host.
One of the most common mosquito-borne causative agents
Once the infective stage is reached, the parasite is ready to
of lymphatic filaria
be transferred into an uninfected human, thus initiating a
Prevalence of infection continues to rise in tropical and
new cycle.
sub-tropical areas due to rapid growth of cities
Habitat of Adult Worms Distribution and transmission of the infection are closely
Serous Cavity Subcutaneous Lymphatic associated with socioeconomic and behavioral factors in
Mansonella Loa loa Wuchereria endemic population, such as poor urban sanitation
perstans bancrofti About 120 million people worldwide are affected, and
Mansonella Onchocerca Brugia malayi more than 1 billion people are at risk mostly in the poorest
ozzardi volvulus areas. Bancroftian filariasis accounts for 90% of cases in
Mansonella 83 endemic countries
streptocerca In the Philippines, 45 provinces are endemic for LF, where
Laboratory Diagnosis there are highest incidences of poverty
Some species of filarial parasites exhibit periodicity, a Anopheles minimus var. flavirostris, the principal vector
phenomenon whereby the parasites are present in the for malaria in the Philippines is also the vector of W.
bloodstream during a specific time period; this feature is bancrofti in Sulu and Palawan
helpful in selecting the appropriate time for specimen Adults are more frequently infected than children, and
collection. there are more infected males than females. This may be
There is evidence to suggest that this periodicity, is connected due to economic activities (e.g., abaca farming) that
to the corresponding vector’s feeding schedule. increase exposure of adult males to mosquito vectors
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CLINICAL PARASITOLOGY
LECTURE / LESSON 3
In the Bicol region, hydroceles are more frequently 1. Mosquito acquires the infection by ingestion of
encountered than elephantiasis of the extremities microfilariae (“small worms”) in the blood meal
Morphology 2.
Wuchereria Bancrofti
Microfilaria: Typical Characteristics at a Glance
Parameter Description
Size range 240-300 μm long
Sheath Present 3. The L3 larvae migrates to the head and
Arrangement of Tip of tail free of nuclei proboscis
nuclei in tail
4. When a mosquito with infective larvae in its
proboscis feeds on a person, the larvae get
deposited on the skin near the puncture site
Development in Man
Note: A large number of infected mosquito bites are required
to ensure transmission to man, around 15,000 infective bites
per person (3-4 bites for a person to become infected)
1. After penetrating the skin, the L3 larvae enter the
A thin and delicate sheath lymphatic vessels and are carried usually to abdominal or
surrounds the organism inguinal lymph nodes, where they develop into adult forms
Numerous nuclei are and mate
contained in the body 2. Adults release thousands of sheathed microfilariae that
Cephalic or anterior end is migrate into the lymphatic and peripheral blood circulation
blunt and round 3. Microfilariae are then ingested when a mosquito has a
Posterior or tail end blood meal
culminates in a point that
is free of nuclei
Wuchereria Bancrofti
Adults: Typical Characteristics at a Glance
Characteristics Adult Female Adult Male
Size 40 to 100 mm 20 to 40 mm
Color White White
Shape Threadlike Threadlike
appearance appearance
(filiform) (filiform)
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Peak hours for specimen collection: between 9:00 PM Typical clinical manifestations are not present, and
and 4:00 AM microfilaria are not found in the blood but may be found in
Subperiodic organisms: sometimes detected throughout the tissues
the day - more prevalent in late afternoon In most cases, lung function is impaired which is
Serologic tests: antigen and antibody detection and PCR commonly misdiagnosed as asthma or tuberculosis
assays If untreated, TPE progresses to chronic pulmonary
Pathology fibrosis and respiratory failure
Brancoftian filariasis: Lymphatic filariasis (W. Bancrofti) Signs and Symptoms
Asymptomatic, acute, and chronic stages, generally LF is characterized by a wide spectrum of clinical
progressing in that order manifestations, with signs and symptoms different from one
- Endemic community: different stages of the disease host to another. The clinical course may be divided into
frequently overlap asymptomatic, acute, and chronic stages.
- Non-endemic areas: initial acute stage followed 1. Some people have no symptoms (Asymptomatic)
directly by a chronic stage in short period of time 2. Acute Symptoms may include:
- Outside regions: “Expatriate Syndrome” - Lymphadenitis and lymphangitis
Lymphatic localization - Lymphangiogenesis
Lymphangiectasia - Epididymitis
Lymphangiogenesis - Funiculitis
Lymphatic insufficiency - leads to increase susceptibility 3. Chronic Symptoms:
to opportunistic infections - Abscesses
Clinical spectrum of lymphatic filariasis includes: - Hyperkeratosis
Asymptomatic microfilaremia - Polyarthritis
Shows no obvious clinical signs of disease - Hydroceles
Acute - Elephantiasis
dermatolymphangioadenitis - Distal lymphedema
(ADLA) Prevention and Control
Most common acute Using personal protection when entering known endemic
manifestation of LF areas
Localized pain, lymphadenitis Destroying breeding areas of mosquitoes
and/or lymphangitis and/or Using insecticides when appropriate
cellulitis and local warmth Educating inhabitants of endemic areas
Bacterial etiology - Group A Mosquito netting and insect repellent are more practical
Streptococcus Dermatolymphangioadenitis and useful
Acute filarial lymphangitis (AFL) (acute lymphatic filariasis) Treatment: Diethylcarbamazine, Ivermectin, Albendazole
Rare manifestation directly caused by adult worms that The use of special boots also known as “Unna’s Paste
died spontaneously Boots”
Characterized by lymphangitis; may be accompanied by Notable Characteristics
mild fever, headache, and malaise Periodicity: Nocturnal (9PM-4AM), Subperiodic
Distal lymphedema may occur - usually mild and Nuclei arrangement: No nuclei at the tip of the tail
reversible. Symptoms are self-limited or generally subside Presence or absence of sheath: Sheathed
without treatment
Lymphedema and Elephantiasis Brugia Malayi
Most common chronic (broog’ee-uh/may-lay-eye)
manifestation which on progression Common name: Malayan filaria
leads to elephantiasis Common associated disease and condition names: Malayan
Lower limbs are commonly filariasis or Elephantiasis
affected but upper limb and male Classification
genitalia may be involved. Females - Kingdom: Animalia
breasts and genitalia may be affected Phylum: Nematoda
but this is relatively uncommon Class: Secernentea
Genito-urinary lesions - Hydrocele Order: Spirurida
Common chronic disease manifestation of Bancroftian Family: Filariidae
filariasis Genus: Brugia
Usually occur after puberty Species: B. Malayi
Chronic epididymitis, funiculitis, lymphedematous Epidemiology
thickening of the scrotal skin, and thickening of the Brugia malayi is a filarial (arthropod-borne) nematode
spermatic cord (roundworm), one of the three causative agents of
In females, lymphedema of the vulva may occur lymphatic filariasis in humans
Tropical pulmonary eosinophilia (TPE) Philippines, Indonesia, Sri Lanka, New Guinea, Vietnam,
Classic example of occult filariasis Thailand, and specific regions of Japan, Korea, and China
are the primary location which the mosquitoes breed
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CLINICAL PARASITOLOGY
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Also infects felines and monkeys
Affects 12.5 million people in Southeast Asia
People living for a long time in tropical or sub-tropical
areas where the disease is common are at the greatest risk
or infection
Malayan filariasis may also be caused by another species of
Brugia, Brugia Timori, first isolated in 1964 on the island of
Timor. Readily distinguishable from B. Malayi, the microfilariae
of B. Timori measure approximately 310 μm. The organism has a
sheath, which is difficult to observe using Giemsa stain and
distinct nuclei in the tip of the tail. The body tissue of this
organism does not bulge around the two nuclei like that of B.
Malayi.
Recent studies in animals show direct evidence that infection
with Brugia can selectively induce CD4+ lymphocyte apoptosis.
Morphology
Brugia Malayi
Microfilaria: Typical Characteristics at a Glance
Parameter Description Diagnostic Stage: Sheathed microfilariae
Size range 200-280 μm long Infective Stage: L3 larvae
Sheath Present Mode of Transmission: Mosquito bite
Arrangement of Presence of two distinct nuclei in the (1) Mosquito takes a blood meal (L3 larvae enter skin)
nuclei in tail tip of the tail; the organism tissue (2) Adults in lymphatics
tends to bulge around each of the two (3) Adults produce sheathed microfilariae that reach the
nuclei blood stream
(4) Mosquito takes a blood meal (ingests microfilariae)
(5) Microfilariae shed sheaths, penetrate mosquito’s midgut,
and migrate to thoracic muscles
(6) L1 larvae
(7) L3 larvae
(8) Migration of L3 larvae to head and mosquito’s proboscis
Laboratory Diagnosis
Ideal host of B. Malayi are humans
Best method for the examination of B. Malayi is through
stained blood films (Giemsa-stained blood)
It also exhibits nocturnal periodicity, which means
the best time for collection is during night time
hours
Knott technique - may also be used (1 ml of blood +
10 ml (2% formalin) > centrifuge (1 minute) > stain
by Giemsa)
Pathology
Lymphatic filariasis: the main disease caused by W.
Brugia Malayi Bancrofti, B. Malayi, B. Timori
Adults: Typical Characteristics at a Glance
Asymptomatic microfilaremia
Characteristics Adult Female Adult Male
Size (length) 53 mm 24 mm
Acute dermatolymphangioadenitis (ADLA) also
Color White White previously called Adenolymphangitis (ADL)
Shape Threadlike Threadlike Acute filarial lymphangitis (AFL)
appearance appearance Lymphedema and Elephantiasis
Life Cycle Genitourinary lesions (e.g., Hydrocele)
B. Malayi carries out its life cycle in two different hosts: Tropical pulmonary eosinophilia (TPE)
Definitive Host: Humans Signs and Symptoms
Intermediate Host: Mosquitoes 1. Infections with B. Malayi are often asymptomatic
Three most common vectors (depending on the location and even with the presence of microfilariae in the blood
animal reservoirs present): 2. Formation of granulomatous lesions
Aedes
3. Chills
Anopheles
4. Lymphadenopathy
Mansonia
Culex
5. Lymphangitis
6. Eosinophilia
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CLINICAL PARASITOLOGY
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7. Eventually the result of elephantiasis of the legs nuclei in tail extend to the tip of tail
8. Elephantiasis of the genitals is possible but less
common
9. Elephantiasis - (skin/tissue thickening) of limbs and
hydrocele (scrotal swelling) infection occurs when
filarial parasites are transmitted through mosquitoes
Note about symptoms:
A condition called tropical eosinophilia or occult
(meaning hidden or not apparent) filariasis is known to
occur in persons who reside in the areas of the world in
which both B. Malayi and W. Bancrofti are endemic.
These patients experience a number of pulmonary and
asthmatic symptoms. The signs and symptoms may be due
to the body’s inflammatory response.
Prevention and Control
The prevention and control measures for B. Malayi are
identical to those for W. Bancrofti
Using personal protection when entering known endemic
Loa Loa
areas
Adults: Typical Characteristics at a Glance
Destroying breeding areas of mosquitoes
Using insecticides when appropriate
Characteristics Adult Female Adult Male
Educating the inhabitants of endemic areas
Size (length) 38 to 72 mm 28 to 35 mm
Treatment: Color White White
Most useful medication - Diethylcarbamazine (DEC)
Shape Cylindrical Cylindrical
Inflammatory drugs may be necessary - inflammatory
threadlike threadlike
reactions are more common after treatment and can be appearance appearance
severe Life Cycle
Notable Characteristics Vector: Chrysops fly (deer fly)
Periodicity: Nocturnal (10PM-4AM), Subperiodic
Nuclei arrangement: Presence of two distinct nuclei in the
tip of the tail
Presence or absence of sheath: Sheathed
Loa Loa
(lo’uh/lo’uh)
Common name: African eye worm or Eye worm (African)
Common associated disease and condition names: Loiasis
Epidemiology
The people most at risk for loiasis (parasite of the eye) are
those who live in the certain rain forests in West and
Central Africa
Rubber plantations are areas where more deer flies may be
found. The flies do not typically enter homes, but they
might be attracted to homes that are well lit
Travelers are more likely to become infected if they are in
areas where they are bitten by deer flies for many months,
though occasionally they get infected even if they are in an
affected area for less than 30 days
Diagnostic Stage: Sheathed microfilariae
In the case of L. loa, the Chrysops fly inhabits Africa
Infective Stage: L3 larvae
especially the rainforest belt region. It is estimated that
Mode of Transmission: Fly bite
infection rates may be over 70% in the areas in which a
(1) Fly (genus Chrysops) takes a blood meal (L3 larvae enter
large vector population exists. A less than 10% infection
bite wound)
rate occurs in regions in which minimal numbers of
(2) Adults in subcutaneous tissue
vectors reside
(3) Adults produce sheathed microfilariae that are found in
Morphology spinal fluid, urine, sputum, peripheral blood, and in the lungs
Loa Loa (4) Fly takes a blood meal (ingests microfilariae)
Microfilaria: Typical Characteristics at a Glance (5) Microfilariae shed sheaths, penetrate fly’s midgut, and
Parameter Description migrate to thoracic muscles
Size range 248-300 μm (6) L1 larvae
Sheath Present (7) L3 larvae
Arrangement of Distinct continuous row of nuclei; (8) Migrate to head and fly’s proboscis
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Laboratory Diagnosis Common associated disease and condition names:
In people who have been bitten by the flies that carry Loa loa Onchocerciasis, River blindness
in areas where Loa loa is known to exist, the diagnosis can be Classification
made in the following ways: Domain: Eukarya
Specimen of choice for the recovery of L. loa Kingdom: Animalia
microfilariae is Giemsa-stained blood (blood smear) Class: Secernentea
Knott technique Order: Spirurida
These samples yield the best recovery rate when collected Family: Onchocercidae
during the midday hours, between 10:15 AM and 2:15 PM Gender: Onchocerca
(10AM-2PM), diurnal periodicity Epidemiology
Identification of the adult worm by a microbiologist or
A roundworm that belongs to the phylum Nematoda
pathologist after its removal from under the skin or eye It is a parasitic life where the human being is the
Identification of an adult worm in the eye by a health care
definitive host
provider First described in 1874 by John O’Neill (Irish physician)
Identification of antibodies against Loa loa on specialized
Responsible for causing Onchocerciasis (severe blindness)
blood test Vector: Simulium blackfly, Black flies (breeds in running
Diagnosis of loiasis can be difficult, especially in light
water)
infections where there are very few microfilariae in the Vector-borne illness
blood. The specialized blood test is not widely available in Distributed primarily to equatorial Africa and Central
the United States. A positive antibody blood test in America
someone with no symptoms means only that the person More than 99% of infected people live in 31 African
was infected sometime in his/her life. It does not mean that countries
the person still has living parasites in his/her body Endemic: East Africa, Zaire, Angola, parts of Mexico,
Signs and Symptoms Colombia, and some areas of Latin America
1. Many people do not develop any symptoms 2017: 20.9 million (infected worldwide)
(asymptomatic), and symptoms usually do not show up for 14.6 million (skin disease)
many months after infection. If you have loiasis, you may 1.15 million (vision loss)
have itchy, non-painful swellings of the body that come and 1.8 million people (no longer require mass drug
go administration)
2. The swellings can show up anywhere though they are more Morphology
common near joints Onchocerca Volvulus
3. You may develop an eye worm that crawls across the Microfilaria: Typical Characteristics at a Glance
surface of your eye Parameter Description
4. Sometimes you may see a worm that crawls under your
Size range 150-355 μm long
skin
Sheath Absent
5. Less common symptoms: itching all over your body,
Arrangement of Do not extend to tip of the tail
muscle pain, joint pain, and fatigue
nuclei in tail
6. Blood tests may show high counts of eosinophils, which
are a type of blood cell that can be associated with parasitic
infections
Prevention and Control
Personal protection measures are essential to stop the
spread of infection
Destroying the vector breeding areas
The use of prophylactic DEC (300 mg taken once a
week), particularly for non-natives visiting endemic areas
Treatment:
Choice of treatment - Surgical
Ideal time of extracting - when they are attempting to
cross the eye or the bridge of nose. Unfortunately, there is
no appropriate time to perform the procedure in advance
Medication of choice - Diethylcarbamazine (DEC)
(Serious side effect may occur such as encephalitis)
Notable Characteristics
Periodicity: Diurnal (10:15AM-2:15PM) Onchocerca Volvulus
Nuclei arrangement: Distinct continuous row of nuclei Adults: Typical Characteristics at a Glance
extending to the tip of tail Characteristics Adult Female Adult Male
Presence or absence of sheath: Sheathed Size (length) 500 mm 25 to 50 mm
Onchocerca Volvulus Other features Vulva: behind 2 spicules
(onk’o-sur’kuh/vol’vew-lus) posterior (unequal length)
Common name: Blinding filaria extremities of Cuticle: more
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CLINICAL PARASITOLOGY
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esophagus layers and its (9) Migrate to head and blackfly’s proboscis
Cuticle: fewer epicuticle is (12-15 months for the development of microfilariae, lays
layers and its wrinkled 1,000 microfilariae) (Life span of female blackfly: 15 years)
epicuticle is Posterior end: Laboratory Diagnosis
protuberances coiled ventrally Multiple Giemsa-stained glass (Skin snips) - Gold
Color White, opalescent, and transparent standard test
Appearance Thin and wire-like - Tissue biopsies
Body Either or different sexes coil up in - Skin snips should be obtained with as little blood as
knots. Posterior end or tail is curved possible
(Onchocerca name) - ID: microfilariae
Nodulectomy
- ID: microfilariae (adult worms) in the tissue
Ophthalmologic examination (Slit lamp)
- Organisms residing in the eye
Serologic methods
PCR: Detect low-level infections
Pathology
River blindness
Visual impairment or sometimes blindness
Chronic dermatitis
Caused by filarial nematode O. volvulus
Dying larvae evoke focal inflammation resulting in
Life Cycle initial dermal microabscesses followed by granuloma
About the Vector formation
Blackfly genus Simulium
Advance stage: pigmentation spots (leopard skin) and
Require well oxygenated water to mature, eggs are laid in
atrophy of skin
rapids in fast flowing rivers and streams
Female blackfly
Signs and Symptoms
1. Earlier stage: Asymptomatic and it takes up to a year for
symptoms to appear and infection to become apparent.
Severe:
2. Skin rashes
3. Extreme itching
4. Bumps under the skin
5. Loss of skin elasticity (thin and brittle)
6. Itchy eyes
7. Skin pigmentation changes
8. Enlarged groin
9. Cataracts
10. Light sensitivity
11. Loss of vision
12. Swollen lymph glands (rare cases)
Prevention and Control
Personal protection measures against biting insects (best
prevention):
- Wearing insect repellent {N, N-Diethyl-meta-toluamide
Diagnostic Stage: Unsheathed microfilariae (DEET)}
Wearing long sleeves and long pants
Infective Stage: L3 larvae
Wear permethrin-treated clothing
Mode of Transmission: Blackfly bite
(1) Blackfly (genus Simulium) takes a blood meal (L3 larvae Treatment: Ivermectin
enter bite wound) Usage/Drug Adult Dose Pediatric Dose
(2) Subcutaneous tissues To kill 150 mcg/kg orally 150 mcg/kg orally
(3) Adults in subcutaneous nodule microfilariae: in one dose every 6 in one dose every 6
(4) Adults produce unsheathed microfilariae that typically are Ivermectin months months
found in skin and in lymphatics of connective tissues, but also To kill female 200 mg orally daily 200 mg orally daily
occasionally in peripheral blood, urine, and sputum adult worms: for 6 weeks for 6 weeks
(5) Blackfly takes a blood meal (ingests microfilariae) Doxycycline
(6) Microfilariae penetrate blackfly’s midgut, and migrate to Notable Characteristics
thoracic muscles Periodicity: Non-periodic
(7) L1 larvae Nuclei arrangement: Do not extend to tip of the tail
(8) L3 larvae Presence or absence of sheath: Absent (No sheath)
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Mansonella Ozzardi Diagnostic Stage: Unsheathed microfilariae
(man”so-nel’ah/o-zar’de) Infective Stage: L3 larvae
Common name: New World filaria Mode of Transmission: Black fly bite, Midge bite
Common associated disease and condition names: None (1) Arthropod takes a blood meal (L3 larvae enter skin
(considered as a nonpathogen) through bite wound) (black fly - genus Simulium) (midge -
Epidemiology genus Culicoides)
Found exclusively in the Western Hemisphere. M. ozzardi (2) Adults in subcutaneous tissues
is known to exist in Central and South America, as well as (3) Adults produce unsheathed microfilariae that reach the
part of West Indies and Caribbean blood stream
The parasite is transmitted to the human host by biting (4) Arthropod takes a blood meal (ingests microfilariae)
midges (Culicoides furens) and black flies (Simulium (5) Microfilariae penetrate arthropod’s midgut and migrate to
amazonicum) thoracic muscles
Morphology (6) L1 larvae
(7) L3 larvae
Mansonella Ozzardi
(8) Migrate to head and arthropod’s proboscis
Microfilaria: Typical Characteristics at a Glance
Microfilariae: blood as well as capillaries and intravascular
Parameter Description
of the skin
Size range 220 μm long
Adult: body cavities, visceral fat, and mesentries
Sheath Absent
Arrangement of Numerous; do not extend to the tip of Laboratory Diagnosis
Microfilariae recovered in peripheral blood
nuclei in tail tail
No specific time for collecting blood sample
Giemsa-stained blood
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Morphology (3) Adults produce unsheathed microfilariae that reach the
Mansonella Perstans blood stream
Microfilaria: Typical Characteristics at a Glance (4) Midge takes a blood meal (ingests microfilariae)
Parameter Description (5) Microfilariae penetrate midge’s midgut and migrate to
Size range About 200 μm long thoracic muscles
Sheath Absent (6) L1 larvae
Arrangement of Numerous; extend to the tip of tail (7) L3 larvae
nuclei in tail (8) Migrate to head and midge’s proboscis
Laboratory Diagnosis
Blood samples (non-sheathed microfilariae)
Non-periodic (can be identified both day and night)
Microscopic examination (Giemsa-stain)
Molecular detection (LAMP)
Serological testing
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