The Blinding Filaria
MEDICAL UNIVERSITY OF CEBU: Nematodes
Nematodes: Tissue Nematodes: Dracunculus medinensis
Common Names:
Guinea fire worm
Serpent worm
Dragon worm
Medina worm
Fiery Serpent of Israelites
Host Information:
Definitive Host: Man
Intermediate Host: Aquatic Crustacean (Copepods), specifically Cyclops
Mode of Transmission:
Ingestion of infected copepods, usually through drinking unfiltered water containing copepods
Historical Notes:
Galen named the disease "dracontiasis" from Greek "draco" meaning dragon or serpent.
Avicenna referred to it as the Medina worm due to its prevalence in Medina.
The technique of extracting the worm, by twisting it on a stick, is believed to have been devised by Moses.
Illustrative Significance:
The image of the "serpent worm" on a stick may have inspired the symbol of Caduceus used by physicians.
Epidemiology of Dracunculiasis
Eradication Status:
Infection has been eradicated in India and throughout Southeast Asia as of 2000.
Current Endemic Regions:
Remains endemic in 13 African countries including a high incidence in Sudan, Niger, etc.
Guinea worm is found in parts of Africa, India, Asia, Pakistan, and the Middle East.
Parasite Biology of Dracunculus medinensis
Adult
Female Characteristics:
Typically located in subcutaneous tissue of extremities (legs, arms, back).
Long, cylindrical body, smooth and milky-white cuticle, resembling white twine.
Blunt anterior end, tapering recurved tail.
Length: Approximately 60-120 cm, diameter: 1-2 mm.
Gravid females contain a large uterus filled with about 3 million embryos; they are viviparous.
Lifespan is about one year.
Male Characteristics:
Rarely observed; significantly smaller than females, measuring 10-40 mm in length and 0.4 mm thick.
Lifespan does not exceed 6 months.
Anterior end coils once.
Larval Stage
Length: 500-750 µm, width: 15-25 µm.
Broad anterior end with a slender filiform tail extending for a third of the body length.
Cuticle exhibits prominent striations.
Motion: Swims using coiling and uncoiling movements.
Life Cycle of Dracunculus medinensis
L1 (larvae) are consumed by a copepod.
Larvae undergo two molts in the copepod, becoming L3 larvae.
Human drinks unfiltered water containing copepods with L3 larvae.
Larvae are released when copepods die, penetrating the stomach and intestinal wall of the host, maturing and reproducing.
Fertilized female worm migrates to the skin surface, causing blister formation and discharging larvae.
L1 larvae are released into the water from the emerging female worm.
Stages of Life Cycle:
Infective Stage: L1 larvae.
Diagnostic Stage: L3 larvae to adult female.
Pathogenicity and Clinical Features of Dracunculiasis
Symptomatology:
No symptoms until the gravid female worm lodges under the skin, preparing to discharge embryos.
The worm's body fluid is toxic, leading to blister formation.
Constitutional symptoms may include nausea, vomiting, intense itchiness, and urticarial rash before blister formation.
Common blister locations: feet between metatarsal bones or on ankles.
Blister fluid is a sterile yellowish liquid containing polymorphs, eosinophils, and mononuclear cells.
Local discomfort resolves with the rupture of the blister and release of embryos.
Rare cases may see the worm migrate to unusual sites like the pericardium, spinal canal, or eyes leading to serious effects.
Duration of Dracunculiasis: Typically lasts between 1-3 months.
Visual Examples:
Figure A: Female Guinea worm inducing a painful blister.
Figure B: After blister rupture, the worm emerges as a whitish filament at the center of a painful ulcer, often secondarily infected.
Laboratory Diagnosis of Dracunculus medinensis
Detection Methods:
Detection of Adult Worm: Found at the base of ulcers.
Detection of Larva: Under microscope examination.
X-ray: Detect calcified worms.
Skin Test: Guinea worm antigen injected intradermally elicits a positive response.
Serological Tests: Evaluate for antibodies in blood tests, indicating eosinophilia. (Utilizing ELISA and IFA methods).
Treatment of Dracunculus medinensis
Initial Treatments:
Antihistamines and steroids can help mitigate allergic reactions in early stages.
Worm Extraction:
No pharmacological treatment; worms are manually extracted by winding on a stick and gradually retracted from the host.
Current Eradication Efforts:
As of 2018, global eradication efforts are reported by the CDC to be within reach.
Pharmacological Options:
Metronidazole, Niridazole, and Thiabendazole have shown usefulness in treatment.
Gnathostoma Spinigerum
Common Name: Gnathostoma (Malayan filarial worm, Brugian filaria)
Host Information:
Definitive Host: Dogs, cats, and other carnivorous animals.
First Intermediate Host: Cyclops.
Second Intermediate Host: Freshwater fish and frogs.
Paratenic Host: Birds, water snakes, and humans.
Infective Stage: Filariform Larvae (L3)
Mode of Transmission: Ingestion of undercooked fish containing the L3 larvae.
Geographic Distribution:
Human cases are primarily reported in areas where raw fish dishes (sushi, ceviche) are popular, especially in Japan, Thailand, Vietnam, and Mexico.
In the Philippines, the three recorded species are G. spinigerum, G. hispidum, and G. doloresi, with G. spinigerum also reported in humans locally.
Morphology:
Small spirurid nematode:
Female measures 25-55 mm, larger than the male.
Male measures about 10-25 mm.
Eggs are oval, brown, unsegmented, with a transparent knob-like thickening at one end.
Life Cycle of Gnathostoma Spinigerum
Unembryonated eggs are passed in feces.
Eggs hatch in water and the larvae (L1) develop.
First intermediate host (Cyclops) ingests L1 larva.
L1 larva molts twice to early L3 larvae in the second intermediate host (freshwater fish or frog).
Second intermediate host ingests the L3 larvae.
Advanced L3 and/or immature adults undergo aberrant migration in the human host.
Adults develop and form tumors in the gastric wall of the definitive host.
Clinical Presentation of Gnathostoma Spinigerum
Clinical Manifestations:
Caused by migration of advanced L3 larvae or immature adults into various tissues.
Initial migration may result in eosinophilia, though it is not universally present in chronic infections.
Cutaneous gnathostomiasis leads to migratory swellings on skin, typically on torso or upper limbs.
Occasional spontaneous emergence or extraction of the parasite near the skin surface.
Visceral Gnathostomiasis:
Involves deeper tissue migration (pulmonary, gastrointestinal, genitourinary, auricular, ocular) and is known as larva migrans profundus.
Neurognathostomiasis can result in potentially fatal eosinophilic meningitis and myeloencephalitis.
Ocular gnathostomiasis has been noted to cause vision loss.
Diagnosis of Gnathostoma Spinigerum
Diagnostic Tests:
Intradermal tests using larval or adult antigens may be utilized.
Lesions may be biopsied to confirm the presence of typical larvae.
Treatment of Gnathostoma Spinigerum
Surgical Intervention:
Incision of lesions followed by larva removal is standard.
Pharmacological Treatments:
Albendazole and mebendazole at high doses have been recommended.
The necessity of treatment for ocular and CNS infections is debatable as no efficacy studies have been published for albendazole or ivermectin.
Filarial Worms
Definition:
Nematodes belonging to the superfamily Filarioidea, slender and thread-like, transmitted by blood-sucking insects.
Filarial worms reside in the subcutaneous tissues, lymphatic system, or body cavities of humans.
Male worms possess unequal spicules and are viviparous, giving birth to microfilariae.
Microfilariae can be detected in peripheral blood or cutaneous tissues based on species differentiation.
Periodicity of Filarial Worms
Definition:
Periodicity refers to the times when microfilariae are most numerous in the bloodstream.
Types of Periodicity:
Nocturnal Periodicity: Highest count at night (e.g., Wuchereria bancrofti).
Diurnal Periodicity: Highest count during the day (e.g., Loa loa).
Non-periodicity: Constant levels day and night (e.g., Onchocerca volvulus).
Subperiodic/Nocturnally subperiodic: Higher counts in late afternoon or at night.
Microfilariae Behavior:
Microfilariae are located in capillaries and blood vessels of the lungs when not in peripheral blood stream.
Life Cycle of Filarial Nematodes
Hosts:
Definitive Host: Humans
Intermediate Host: Blood-sucking arthropods where microfilariae develop into infective larvae.
Larvae Migration:
Once inside humans, larvae migrate to tissues for final developmental stages (up to 1 year).
Adult worms can lodge in lymphatics, subcutaneous tissue, or internal body cavities.
Human Pathogenic Filarial Species
Pathogenic Species Overview:
Eight filarial species infect humans; six are pathogenic.
Classification:
Lymphatic Filariasis:
Wuchereria bancrofti
Brugia malayi
B. timori
Subcutaneous Filariasis:
Loa loa
Onchocerca volvulus
Mansonella streptocerca
Serous Cavity Filariasis:
M. ozzardi - virtually non-pathogenic
M. perstans - virtually non-pathogenic
Wuchereria bancrofti
Common Name: Bancroft’s Filarial Worm
Host Information:
Definitive Host: Humans
Intermediate Host: Female mosquitoes (Aedes, Culex, Anopheles).
Historical Context:
Disease first reported by Wucherer in 1868, with microfilariae identification in Calcutta by Lewis in 1872.
Manson's work in 1876 identified the Culex mosquito vector and demonstrated nocturnal periodicity.
Epidemiology:
Distribution in tropics and subtropics, particularly sub-Saharan Africa, Southeast Asia, India, and Pacific islands.
Highest incidences in India, particularly noted.
Parasite Biology of Wuchereria bancrofti
Adult Characteristics
Male:
Measures 25-40 mm x 0.1 mm
Curved posterior end with spicules of unequal length.
Female:
Larger (70-100 mm x 0.25 mm), posterior end straight.
Viviparous, releasing sheathed microfilariae into lymph.
Microfilariae
Size:
Ranges from 250-300 µm in length, 6-10 µm thick.
Characteristically sheathed with a tail that is free of nuclei at the tip.
Life Cycle of Wuchereria bancrofti
Mosquito takes a blood meal.
Adults reside in lymphatics.
Mosquito ingests microfilariae.
Microfilariae penetrate mosquito's midgut and migrate to thoracic muscles.
Adults produce sheathed microfilariae that enter peripheral circulation.
Infective Stage: L3 larvae
Diagnostic Stage: Microfilariae
Pathogenicity and Clinical Features of Wucheriasis
Presentation Types:
Classical Filariasis (Lymphatic filariasis): Causes severe lymphatic damage leading to chronic limb and genital swelling.
Occult Filariasis (Meyers Kouwenaar syndrome): Microfilariae absent in peripheral blood despite production, presenting hypersensitivity reactions.
Classical Filariasis
Visual Examples:
Presence of hydroceles in affected individuals.
Clinical Consequences:
Lymphorrhagia noted as rupture of lymph varices leading to various chylous conditions (chyluria, chylous diarrhea, etc.).
Occult Filariasis
Clinical Features:
Massive eosinophilia (30-80%), hepatosplenomegaly, pulmonary symptoms including nocturnal cough and dyspnea.
Associated conditions like arthritis, glomerulonephritis, thrombophlebitis, and tenosynovitis are possible but classical features of lymphatic filariasis are absent.
Tropical Pulmonary Eosinophilia
Manifestation:
Low-grade fever, weight loss, pulmonary symptoms (nocturnal cough, dyspnea).
Characteristic high eosinophil count (>3000 µm, potentially reaching >50,000).
Radiographic appearances similar to miliary tuberculosis.
High levels of serum IgE and filarial antibodies observed, responsive to diethylcarbamazine (DEC).
Laboratory Diagnosis of Wuchereria bancrofti
Detection Methods:
Direct Detection:
Identification of microfilariae in blood smears, both thick and thin, stained with Giemsa.
Techniques include acridine orange and microhematocrit tube methods.
Indirect Evidence:
Eosinophilia in blood, elevated serum IgE levels.
Detection of adult worms via lymph node biopsy, X-ray, high frequency ultrasound.
Immunodiagnosis:
Antigen detection methods (ELISA, ICT) provide high sensitivity and specificity (93-100%) for acute cases.
Antibody detection methods (CFT, IHA, IFA) have lower sensitivity.
Knott's Technique:
Utilized for low microfilariae counts, involving formalin and centrifuge steps for isolation.
Treatment for Wuchereria bancrofti
Pharmacological Interventions:
Diethylcarbamazine is the drug of choice.
Ivermectin effectively kills microfilariae but doesn't impact adult worms.
Tetracyclines (e.g., doxycycline) inhibit worm fertility by targeting the essential endosymbiotic bacteria, Wolbachia.
Surgical interventions are recommended for hydroceles.
Brugia malayi
Common Name: Malayan filarial worm
Host Information:
Definitive Host: Man
Intermediate Hosts: Mosquito vectors (Mansonia, Anopheles, Aedes).
Epidemiology:
Distribution is related to mosquito breeding areas in the Philippines, Indonesia, Sri Lanka, New Guinea, Vietnam, Thailand, and specific regions in Japan, Korea, and China.
Additionally infects felines and monkeys as secondary hosts.
Parasite Biology of Brugia malayi
Adult Characteristics
Similarity to W. bancrofti:
Generally smaller size than W. bancrofti.
Microfilariae
Notable Features:
Smaller size than W. bancrofti with kinks and secondary curves.
Sheath present; nuclear tail arrangement shows two distinct nuclei.
Life Cycle of Brugia malayi
Mosquito takes a blood meal.
L3 larvae penetrate skin.
Adults reside in lymphatics.
Mosquito ingests microfilariae.
Microfilariae shed sheaths, penetrate mosquito's midgut, and migrate to thoracic muscles.
Clinical Features of Brugia malayi
Asymptomatic Nature:
Infections often remain asymptomatic despite microfilariae presence.
Delayed Symptoms:
Fevers may develop months to years after initial infection.
Other Symptoms:
Formation of granulomatous lesions, chills, lymphadenopathy, lymphangitis, and eosinophilia; potentially leading to elephantiasis.
Clinical Presentation:
Similar complications to those seen in W. bancrofti, but mostly localized to limbs.
Mansonella ozzardi
Common Name: New World filaria
Host Information:
Definitive Host: Man
Intermediate Hosts: Midges, genus Culicoides, blackflies, genus Simulium.
Epidemiology:
Found in North America, Central and South America, and parts of the Caribbean.
Morphology of Mansonella ozzardi
Microfilariae
Size Range: 220 µm in length, with blunt anterior end; no sheath.
Nuclei Arrangement: Numerous; they do not reach the tail tip; no periodicity in the blood.
Adult Worms
Size: Female 65-80 mm; Male 32 mm.
Clinical Symptoms of Mansonella ozzardi
Symptomatic Infections: Generally mild, often asymptomatic, may include fever, pruritis, arthralgias, headache, rash, lymphadenopathy, edema, pulmonary symptoms; common eosinophilia.
Corneal Lesions: Observed in Brazil with some infections.
Laboratory Diagnosis of Mansonella ozzardi
Blood Recovery: Microfilariae may be found in peripheral blood; the organism is nonperiodic and can be collected any time.
Microscopic Examination: Giemsa-stained microscopic examination necessary for identification of characteristic features.
Treatment of Mansonella ozzardi
Asymptomatic Cases: Generally not treated; treatment necessary typically involves ivermectin.
Diethylcarbamazine: Proved ineffective against this species.
Mansonella perstans
Common Name: Acanthocheilonema, Dipetalonema, or Tetrapetalonema perstans.
Host Information: Definitive Host: Man; Intermediate Hosts: Midges, genus Culicoides.
Epidemiology: High infection rates in areas endemic to the Culicoides midge, notably in Africa, Caribbean Islands, Panama, and Northern South America.
Morphology of Mansonella perstans
Microfilariae
Size: Approx. 200 µm in length. Sheath is absent; nuclei extend to the tip of the tail.
Adult Worms
Size: Female 82 mm; Male 43 mm. Resides in peritoneal, pleural cavities, and mesentery.
Clinical Symptoms of Mansonella perstans
Symptomatic Presentation: Generally minor allergic reactions or no symptoms; moderate eosinophilia.
Potential Symptoms: Calabar swellings, headaches, edema, lymphatic discomfort, and pain.
Laboratory Diagnosis of Mansonella perstans
Blood Testing: Preferred method at any time due to the non-periodic nature of the species.
Treatment of Mansonella perstans
Asymptomatic Findings: Often left untreated.
Preferred Treatment: Diethylcarbamazine (DEC) when needed; may require multiple treatments; mebendazole is an effective alternative.
Mansonella streptocerca
Common Name: Old World filaria.
Host Information: Definitive Host: Man; Intermediate Hosts: Midges of genus Culicoides.
Epidemiology: Found in tropical regions of West and Central Africa.
Morphology of Mansonella streptocerca
Microfilariae
Size: 180-240 µm by 3 to 5 µm, absent sheath; nuclei extend to the tail tip.
Adult Worms
Size: Females approximately 27 mm; males measure 50 µm in diameter.
Clinical Symptoms of Mansonella streptocerca
Symptomatic Manifestations: In general, most infections are asymptomatic; associated symptoms can include pruritis, dermatitis, and pigmentation lesions.
Laboratory Diagnosis of Mansonella streptocerca
Microfilariae Detection: Observed in skin snips, analysis through microscopic examination is required.
Onchocerca volvulus
Common Name: Convoluted filaria; also known as