Blood & Tissue Nematodes

Blood & Tissue Nematodes

  • Overview

    • Also known as filarial nematodes

    • There are 8 known species of filarial nematodes that use humans as definitive hosts, subdivided based on the anatomical location from which they cause pathology:

    • Lymphatic Filariasis

      • Wuchereria bancrofti

      • Brugia malayi

      • Brugia timori

    • Subcutaneous Filariasis

      • Loa loa (African eye worm) – Loiasis

      • Onchocerca volvulus – Onchocerciasis

      • Mansonella streptocerca

      • Mansonella ozzardi

    • Serous Cavity Filariasis

      • Mansonella perstans – Mansonellosis

  • General Characteristics of Filarial Nematodes

    • Female Worms:

    • Produce microfilariae (early larvae) which circulate in the blood except:

      • O. volvulus & M. streptocerca: Skin

      • O. volvulus: Invades the eye

    • Transmission:

    • Microfilariae infect biting arthropods (Table 3: Arthropod vectors of each microfilariae)

    • Mode of Transmission:

    • Bite of a blood-feeding arthropod vector (mainly mosquitoes and blackflies)

A. Geographic Distribution of Filarial Worms

  • Table 1: Geographical distribution of each filarial worm

    • Wuchereria bancrofti: Tropical areas worldwide

    • Brugia malayi: Limited to Asia

    • Brugia timori: Some islands of Indonesia

    • Onchocerca volvulus: Mainly in Africa, with additional foci in Latin America & Middle East

    • Loa loa and Mansonella streptocerca: Africa

    • M. perstans: Africa & South America

    • M. ozzardi: American continent

B. Generalities of Filarial Nematodes

  • Definitive Host: Man

  • Intermediate Host (Vector): Arthropod

  • Diagnostic Stage: Microfilaria

  • Infective Stage: 3rd stage larvae (L3)

  • Mode of Transmission: Bite of arthropod vector

  • Diagnosis: Thick blood smear

  • Life Cycle:

    1. Infective larvae are transmitted by infected biting arthropods during a blood meal.

    2. Larvae migrate to the appropriate site of host’s body where they develop into microfilariae-producing adults.

    3. Adults dwell in various human tissues (see Table 2) where they can live for several years.

    4. Inside the arthropod, microfilariae develop in 1-2 weeks into infective filariform (3rd stage or L3) larvae.

C. Periodicity of Microfilariae

  • Definition: Fluctuations in numbers of microfilariae present in the peripheral blood during a 24-hour period.

  • Table 4: Periodicities of some filarial worms

    • Nocturnally periodic: W. bancrofti and B. malayi (found in the blood during nighttime hours but absent at other times)

    • Diurnally periodic: Loa loa (present only during certain daytime hours)

    • Nonperiodic or aperiodic: Mansonella spp. (circulate in the blood throughout the 24-hour period without significant changes in their numbers)

    • Subperiodic: B. malayi (normally present in the blood at all hours but whose density increases significantly during either the night or day)

D. Blood Nematodes - Locations

  • W. bancrofti and B. malayi: Lymphatic vessels and nodes

  • O. volvulus: Nodules in subcutaneous tissues

  • Loa loa: Subcutaneous tissues where it migrates actively

  • M. streptocerca: Dermis and subcutaneous tissue

  • M. perstans: Body cavities & surrounding tissues

  • M. ozzardi: Subcutaneous tissue and mesenteries

II. Diagnosis of Filarial Nematodes

  1. Microscopic Finding of Microfilaria in Blood

    • Thick and thin smears are prepared from fingerstick blood, recommended due to microfilariae concentration in the peripheral capillaries.

    • Thick blood smears for W. bancrofti and B. malayi are taken between 8pm – 4am (due to nocturnal periodicity), stained with Giemsa or H&E.

    • B. malayi may also have subperiodic periodicity; best time for collection is at night, though may also be collected during the day.

    • In chronic infections, microfilariae may not be demonstrable in the peripheral blood due to:

      • Low intensity of infection

      • Dead worms

      • Obstructed lymphatics

  2. Concentration Methods for Low Intensity Infections:

    • An anticoagulated (EDTA) venous blood sample of about 1mL can be concentrated via:

      • Filtration using nucleopore filter (Millipore® or Nucleopore®)

      • Centrifugation using Knot’s method (centrifugation of blood sample lysed in 2% formalin)

  3. DEC Provocative Test:

    • A single dose of 3mg/kg of DEC stimulates microfilariae to surface in peripheral circulation (this allows for daytime collection).

    • Sensitivity is low and acceptability is poor.

  4. Detection of Circulating Filarial Antigens (CFA):

    • Preferred method as it can detect latent infections, even when microfilaremia is low and variable.

    • Primarily conducted with immunochromatographic card tests, especially with W. bancrofti antigens, which are very sensitive and specific, eliminating the need for laboratory facilities.

  5. Examination of Skin Snips:

    • Identifies microfilariae of Onchocerca volvulus and Mansonella streptocerca, obtained using a corneal-scleral punch or scalpel and needle.

    • Sample incubated for 30 minutes to 2 hours in saline or culture medium, then examined for microfilariae migrating from the tissue to the liquid phase.

  6. Other Diagnostic Approaches:

    • Molecular xenomonitoring of parasites in pools of mosquitoes and detection of exposure in children via antibody detection

    • Molecular diagnosis via PCR for W. bancrofti and B. malayi.

    • Ultrasonography, contrast lymphangiography, lymphscintigraphy may demonstrate live worms in lymphatics.

E. Wuchereria Bancrofti and Brugia Malayi

  • Also known as:

    • Bancrofti’s Filarial Worm

    • Malayan Filarial Worm

  • Vector: Mosquitoes

  • Habitat: Lymphatic tissues/organs

  • Pathology: Lymphatic filariasis

  • Diagnosis: Thick blood smear; immunochromatographic card tests

  • Drug of Choice: Diethycarbamazine (DEC)

Wuchereria bancrofti

  • Causes chronic disfiguring disease that may present as:

    • Lymphedema

    • Elephantiasis

    • Hydrocele

Brugia malayi

  • Causes chronic infection that presents with:

    • Lymphedema

    • Elephantiasis

  • Infection with these filarial parasites also causes:

    • Acute fever

    • Inflammation of the lymphatic system

    • Tropical pulmonary eosinophilia (TPE)

Life Cycle of Wuchereria bancrofti

  • Vector: Aedes, Culex, Anopheles

  • Adult male and female worms reside tightly coiled in nodular dilated nests (lymphangiectasia) in lymph vessels and in sinuses of lymph glands.

  • Adult Location:

    • Lower extremities

    • Inguinal lymph nodes

    • Epididymis in males

    • Labia in females

  • Infection of Definitive Host (Man):

    • During a blood meal, infected mosquito introduces 3rd stage filarial larvae onto the skin, actively penetrating into the bite wound, developing into adults commonly residing in lymphatics.

    • Microfilariae produced by adults migrate into lymph and blood channels.

  • Infection of Intermediate Host (Mosquito):

    • Mosquito ingests microfilariae during blood meal; microfilariae lose their sheaths and work through the proventriculus and cardiac portion to thoracic muscles.

    • Develop into 1st stage larvae (L1) then into 3rd stage infective larvae (L3) within 6 to 20 days.

Brugia malayi

  • Similar life cycle to W. bancrofti:

    • Vector: Mansonia

    • Development of microfilariae to L3 takes 2 weeks

    • Maturation of L3 to adult takes 3 to 9 months

Pathogenesis and Clinical Manifestations of Lymphatic Filariasis (LF)

  • Second leading cause of permanent disability affecting both physical and psychological aspects.

  • Clinical Course:

    • Asymptomatic, acute, chronic stages, generally progressing in that order

    • Asymptomatic Stage:

      • Carries a significant number of microfilariae in peripheral blood with no clinical manifestations.

      • Occurs among individuals with a highly downregulated immune system.

    • Acute Stage:

      • Early manifestations can include fever and inflammation of lymph glands, especially those of male genital organs, arms, and legs.

      • Recurrent attacks with redness and swelling of limbs, possibly accompanied by vomiting and headache.

    • Chronic Stage:

      • Risks increase with exposure to secondary infections (Wolbachia) and magnitude of immune response.

      • Various lymphatic dilations may develop with chronic degeneration of surrounding tissues, leading to lymphedema or elephantiasis.

Treatment for Lymphatic Filariasis

  • Drug of Choice: Diethycarbamazine (DEC)

  • Effective against both microfilaria and adult worms but some strains may show resistance.

  • A regimen of 6mg/kg for 12 consecutive days is more effective than a single dose.

  • Additional drugs include Ivermectin, Albendazole, and Doxycycline:

    • Ivermectin: Paralyzes and immobilizes microfilariae.

    • Doxycycline: Targets endosymbiont Wolbachia, leading to long-term sterility and death of adult worms.

Epidemiology of Lymphatic Filariasis

  • High incidence in tropical and subtropical countries; driven mainly by urban expansion.

  • Infective prevalence higher among adults than children; and higher in males due to economic activities.

Loa loa - African Eye Worm

  • Pathology: Subcutaneous filariasis (Loiasis)

  • Lives in subcutaneous tissue, often visible when migrating through conjunctiva.

  • Diagnosis & Treatment:

    • Often diagnosed through skin snips. Treatment options exist, though prevention strategies primarily focus on vector control measures.

Mansonella spp. - General Characteristics

  • Usually asymptomatic except sometimes can cause skin lesions, arthritis, and eosinophilia.

  • Diagnose primarily via blood samples or skin snips.

Onchocerca volvulus - River Blindness

  • Pathology: Causes onchocerciasis, a significant cause of blindness.

  • Transmission: Vector is the blackfly (Simulium).

  • Treatment focuses on controlling symptoms and managing social impacts due to physical deformity from infections.

Treatment for Tissue Nematodes

  • Various drug regimens depending on the specific nematode, with a focus on managing symptoms of infection and controlling parasite populations.

References

  • Tables and figures referenced described life cycles, identifying differences in morphology, habitats, and physiological effects on various hosts.

  • Understanding these factors is critical for diagnosing and targeting interventions against these nematodes.