Nematode Parasites of the Respiratory System
Morphology and Biology
- Small worms with superficial resemblance to hookworms
- Dioecious and sexually dimorphic
- Males rudimentary copulatory bursa
- Generally feed on host cellular tissue, not blood
- Most develop to infective stage in obligate intermediate host
Dog Lungworms
Filaroides hirthi
Filaroides osleri
Filaroides hirthi
- Adults in lung parenchyma
- PPP = ~35 days (5 wks) post infection
- L1 infective stage
Filaroides osleri
- Adults in trachea and bronchi
- Form nodules detectable @ 2 months
- PPP ~6-7 months post infection
Filaroides spp. Life Cycle
- L1 passed in feces of infected mother called COPROPHAGY: normal ingestion of feces by animals.
- Puppies infected by ingestion of L1. May be through ingestion of larvae in vomitus of mother.
- L1 ovoviviparous eggs hatch w/in uterus of adult female worms
- Tracheal migration by the hepatic circulation
Diagnosis
- Baermann exam
- Zinc sulfate flotation
- KINKED TAIL w/ DORSAL SPINE
- Larvae ~ 350um.
- Shed intermittently, collect feces for 5 days is best
- Active migration of live larvae out of feces to water and settle at the bottom stem of glass.
- Microscopic wet mount
Clinical significance
- Include hard, dry coughing
- Stimulated by cold air or exercise
- Chronic and unremarkable
- Possible obstruction of trachea
- At necropsy, focal areas of necrosis in the parenchyma of the lung lobes
- Severe disease in hyper infected and immunocompromised
Treatment and prevention
- Tx difficult with variable results
- Efficacious chemotherapy: cessation of symptoms, cessation of larval shedding, clinical improvement.
- FBZ SID (once daily) for 7 days resolved, but failed to remove worms SID for 14 days
- IVM 1000ug/kg twice = 74% effective
- 5-10% of treated dogs continue to shed larvae
- *Prevention by avoiding contact w/ infective larvae (easier said than done)
Angiostrongylus vasorum
French heartworm
- Small worms living in the right heart/pulmonary artery
- Widespread in Europe.
- Associated with pulmonary thrombosis, clotting disorders, hemorrhage from deposited eggs and larvae.
Treatment
- Milbemycin weekly (4x)
- Standard heartworm prophylactic dose
- Not zoonotic
Wildlife
-Incidental finding in Red Fox (Vulpes vulpes) from West Virginia
-Did not seem to be associated with significant pathology
Others: Angiocalus gubernaculatus.
Angiostrongylus costaricensis
- Living in mesenteric arteries
- Spread in Florida, deaths in primate colonies
Angiostrongylus cantonensis
- Associated with neurologic disease from larvae in meninges and inflammatory response
- Naturally occurring in rats in Southeast Asia
- Spread to North America (New Orleans). Fatal case Howler monkey in zoo.
- 1st human case in 1995
Zoonotic Angiostrongylus cantonensis
- Definitive host: RATS
- Intermediate host: Grasshopper
- L1 shed in feces. IH ingests L1
- L3 infective stage in the IH
- Incidental ingestion of gastropod larvae by humans via infected produce
Symptoms in TN
- Eosinophilic meningitis in infant
- Tx: ABZ w/ corticosteroids
Aleustrongylus abstrusus
Cat lungworm
Indirect life cycle
- L1 passed in feces ingested by snail/slug
- IH: snail, gastropods
- L3 infective stage in birds
- Paratenic host: Birds, mice
- PPP= 5-6 weeks
Pathogenesis
- Tiny worms parasitic in terminal bronchioles and alveolar ducts
- Eggs are laid in lung parenchyma
- “nests” of worms appear as small nodules w/ associated inflammatory response and focal necrosis
- coughed up and swallowed, then passed in feces.
Clinical significance
- Prevalent in free-ranging cats
- Often clinically in apparent and unremarkable
- Occasionally seen in routine fecal exams
- Coughing, dysorexia, cough, dyspnea, polypnea in severe cases.
- Fatal complication w/ anesthetic associated deaths in shelter-run spay/neuter program 9%
Diagnosis
- Fecal Bearmann exam
- Zinc sulfate flotation
- Larvae ~350um, kinked tail w/ dorsal spine
Treatment
- FBZ SID 3-15 days
- Prevention by reducing predation of paratenic host and infective larvae
Troglostongylus sp.
Lungworm
- Agent of feline respiratory disease in Europe and Mediterranean
- Indirect life cycle
- L3 infective stage in snail (IH)
- Various species occur in frontal sinuses, bronchi, and trachea of cats.
- Does not appear to occur in pet cats in USA
Capillaria spp.
- Small worm with whip-like anterior ends
- Parasites of all classes of vertebrates, reptiles, amphibians, birds, mammals.
Life cycle
- Variable
- simple direct
- Facultative indirect w/ paratenic host
- Obligate indirect w/ intermediate hosts
Species of veterinary importance
-Respiratory tract/sinuses
Capillaria (Eucoleus) boehmi, C. aerophilus
-Urinary tract
C. plica (Pearsononema), C. feliscati
-Alimentary tract/intestine
C. (Aonchotheca) puttori
Cat and Dog Lungworms
-Capillaria (Eucoleus) aerophila
Adults in bronchi
-Capillaria (Eucoleus) bohemia
Adults are in nasal sinuses
-Small worms (25 to 35mm)
Life Cycle
-Facultative indirect (earthworm as paratenic host)
Clinical signs
-Bronchopneumonia, rattling wheezy respiration, coughing, ADR.
Diagnosis by fecal flotation
- control by environmental hygiene
- successfully treated
- Macrocyclic lactones drugs
Lungworm parasites of Domestic Livestock
Muellerius capillaris
Metastrongyloidea
- Larvae, obligate indirect life cycle
- Tiny parasites deeply embedded in the respiratory tissue (parenchyma) of goats and sheep.
- L1 passed in feces
- L3 infective stage, tracheal migration to lungs
- Adults reproduce and begin passing larvae ~ 4 weeks Post infection
Clinical importance
- clinical symptoms result from heavy infections in immunocompromised animals
- Coughing and rapid breathing, weight loss, etc.
- 1st stage larvae easily differentiated from Dictyocaulus by kinked tail
- Macrocyclic lactone @ 200-500 um/kg
Lungworm parasites od Domestic Livestock
Dictyocaulus spp. (no kinked tail or dorsal spine)
Trichostrongyloidea
Direct life cycle
- Horse and donkey (D. arnfeldi)
- Cattle (D. viviparus)
- Sheep and goats (D. filaria)
- L1 passed in feces
- Bearmann test
- Infective stage in ~5days
- Ingested larvae migrates to lungs via mesenteric lymphatic nodes and thoracic duct
- Adults reproduce ~4 wks PI
Clinical sings
- light infections often asymptomatic
- Horses more susceptible than donkeys
- Heavy infections occlude airway and obstruct airflow.
- Decreased eating/weight gain resulting from stress to breathe
- Host resistance is function of age, vigor, genetics, established infection, acquired immunity
- Environmental conditions: moderate temperatures, damp pastures.
- Successful treatments with macrocyclic lactones
Metastrongylus sp.
Swine lung worm
- commercial confined operations not much of an occurrence
- free-range need to maintain awareness
Direct, Facultative indirect life cycle
- Most often in bronchioles and trachea
- Thread-like resembles hookworms
- 3 species
- Embryonated eggs passed in feces
- L3 infective stage (infected earthworm)
- Migrate to lung to reproduce
- PPP 25 days
Metastrongylus elongatus
- diagnosis by fecal flotation
- superficial resemblance to Ascaris suum (40x50 um)
- thick mamillated shell, single cell, larvated egg in feces or sputum.
Clinical significance
- Alveolitis/broncholitis
- Chronic and paroxysmal coughing
- Unthriftiness failure to meet ADG production goals
- Secondary pneumonia with dyspnea and abdominal respiration (thumps)
- Both parasitisms may occur in pasture contaminated with Ascaris and Metastrongylus
Control and prevention
- Prevent ingestion of paratenic/intermediate host
- nursing piglets may get larvae or eggs from sow
- FBZ effective
- Ivermectin, Doramectin ~21, 24 days
Heartworm Infection and Disease in Dogs
Dirofilaria immitis
Canine heartworm
Dirofilaria immitis
- Veriform embryonic stage called microfilaria
- Diagnostic for infection status
- Dogs infected by mosquitoes
- Mosquitoes harbor infective larvae
- The larvae migrates in SQ tissue, colonize pulmonary artery ~70-100 days PI and become reproducing adults
- Microfilariae begin circulating 6 months post infection
- PPP 6 months
- Female mosquitoes feeding on microfilaremic dogs complete the life cycle
- Development to infective stage in the mosquito ~ 14 days @>57F (L3)
- Transmission to new host (L4) infective to dog
- Worms live in pulmonary arteries and right side of heart
- Seasonal and perhaps year-round transmission
- Wild canids opportune reservoir
- TN top 10 state
Clinical signs
- Immune stimulation of host tissues by adult worms and their products. Obstructive fibrosis, pulmonary and endothelial damage, impaired blood flow, reduced cardiac output.
- Hypertension, hypertrophy, enlargement of the right side of heart. Reverse D radiograph profile. Pulmonary infiltrates
Microfilaria immitis
Pathogenesis
**The most significant veterinary health issue in companion animal medicine
-Kidney disease from obstruction of glomeruli
- Antigen-antibody complexes
- Microfilaria (embryonic stage, not larvae)
- Wolbachia pipientis (gram negative bacteria) endosymbiotic. Incites inflammation, present in arthropod vectors. Transmitted in utero from adult female worms to their microfilariae.
- Larvae pushes through right atrium and vena cava
- Interference of blood flow and AV valve
- Jaundice, hemoglobinemia and hemoglobinuria
- Fatal if not attended promptly
- Uncontrolled hemorrhaging
- Secondary host response triggered by various infectious disease events
- Heartworm induced pulmonary thromboembolism
Heartworm Preventatives
DEC: Diethyl Carbonamide
- DEC + Oxibendazole, extremely microfilarcidal
- Targets L3 at molt to L4
- Given by mouth SID
- Has plus for enteric nematode parasite control
- Anaphylactic shock**
Currently
Monthly administration
**Kills L3 and early L4 larvae acquired last 30 days since last treatment
- Heartguard: IVM, Pyrantel pamoate
- Sentinel: Milbemycin, Lefenuron
- Advantage multi: Moxidectin, Imidacloprid
- Trifexis: Mibemycin oxime, Spinosad
- Simparica Trio: Pyrantel, Moxidectin, Sarolaner
- Revolution: Seleamectin
Heartworm susceptibility to Macrocyclic lactone drugs
and Melarsomine dihydrochloride adulticide therapy
0-30 days: L3-L4 (susceptible)
30-80/120 days: Susceptiable gap
120-210 days: Melarsomine susceptible, Adult (antigen positive)
Emerging Drug Resistance
- Evidence monthly HW prophylaxis failure associated with over expression of the P-glycoprotein (aka MDR1) . Heartguard, Interceptor
- Prevents macrocyclic lactone from crossing BBB
- *Annual testing important
- *Mississippi Delta: high rates of transmission
Lack of Effectiveness, Gaps in Owner Compliance
-Geographic isolates known to over express P-gp w/LOE to HW preventative drugs
- Establish the HW status of all pets at least once a year. Antigen and microfilaria testing
- Discuss heartworm prevention at every visit
- Good compliance
- Poor compliance-Review risks
- Keep track of purchase history
- Online reminders
- *heartworm compliance tool: window of infection
Diagnosis of Canine Heartworm Disease
Clinical presentation adult, >6 mts of age.
- exercise intolerant
- Trouble breathing
- Lays around
- Outdoor animal
- No consistent history of HW prophylaxis
Blood test (Filter test)
- Based on examination of fresh blood collected EDTA (purple tube)
- Blood lysed in ~2% Formalin
- Microfilaria are concentrated on membrane
- Membrane examined microscopically on glass slide
Blood test (Knott’s test)
- Fresh blood, EDTA purple top tube…same as above
- Microfilaria are concentrated by centrifugation
- Wet mount examined on microscope slide
Characteristics of microfilaria
- ~280-320 um length
- Width 601-7.2um
- Head is tapered
- Tail is straight
Acanthocheilonema reconditum (aka Dipetalonema)
- Nonpathogenic
- ~215-270 um length
- ~4.7-5.8 um width
- Head is blunt, tail is often hooked
- *If not measure 50% risk of misdiagnosis
- Technology shift in the last 30 years.
- Antibody testing, antigen testing
- *Antigen testing is the most sensitive method
Diagnostic testing
Serologic testing
- Test kits
- ELISA
Sensitivity: ~95% the ability of the test to detect subjects with infection: set amount of antigen available for detection. Number of worms 2 or more is plenty. Sex ratio infection, maturity of worms.
Tests with poor sensitivity susceptible to many false negative.
Specificity: the ability of the test to detect those without infection. Poor specificity leads to excessive false positives
Predictive value: the probability that the test correctly discriminates between subjects with and without infection. Dynamic property. Sensitivity, specificity, and prevalence of infection in the population.
Low prevalence correlated with poor positive predicted value (excessive false positives)
- **Clinical signs = greatest PPV (possible predicted value)
- **Predictive value > with disease prevalence
Treatment of Canine Heartworm Infection
- Mitigate the clinical condition of the affected animal
- Arrest the disease process by eliminating adult worms and their migrating stages
- Eliminate microfilaria that are infectious to mosquitoes and susceptible host…
Three phases
- Pre-adulticide clinical evaluation and treatment: removal of HW larvae and Wolbachia
- Adulticide treatment: Melarsomine dyhydrochloride to kill adults worms>100 days post infection in pulmonary artery. 2-3 injections protocol
“Slow kill” alternatives: Not endorsed by AHS, CAPC, or FDA labeled - Post-adulticide evaluation and treatment to eliminate microfilaria. Antigen testing to verify treatment effectiveness. Microfilaria testing and treatment
Early Treatment 0-30 days
- Pre-adulticide clinical evaluation
- Classify patients: asymptomatic or asymptomatic. Mild, moderate or severe.
- Blood chemistry panel
- Radiographic evaluation
- **Blood examination for microfilariae
- Tx 30-45 days later to remove migrating HW: any monthly prophylactic acceptable
- IVM, Selamectin, Milbemycin, or Moxidectin
- *Tx to remove Wolbachia: Doxycycline @ 10mg/kg BID, 4 wks.
Early Treatment 0-30 days
- Same as above except
- IVM and Selamectin for mild results
- 2nd monthly prophylactic treatment
Adulticide Treatment Day 60-90
-Removal of adult worms in pulmonary artery/right ventricle: Immiticide, Diroban (Melarsomine Dihydrochloride)
-Safe, highly efficacious 90-98%
-Only effective against adult worms in pulmonary artery @ 100 days post-infection
-Low risk of hepatotoxicity
-Pulmonary thromboembolism risk
-Immiticide treatment regimens:
Classic FDA lebeled: 2 injections (IM deep epaxial lumbar). SID 24 hours apart; stabilized class 1 and class 2.
New recommended (AHS, CAPC); 3 total injections without regard to HWD class: SID once @ day 60 following initial diagnosis, Repeat (2x) @ 24 hrs intervals, Day 90 & 91.
***Cage rest and leash walk for 6 to 8 weeks. Risk of thromboembolism.
“Slow kill” Adulticidal treatments
- Removal of adult worms in pulmonary artery/ right ventricle
- Original IVM, efficacious over extended period 71% @24 mts, 95% @ 29 mts
- HW associated inflammatory disease still on-going
New “slow kill”
- IVM SID q 15 day intervals for 6 mts
- Doxycycline SID for 30 days
- Efficacy 78% @ 36 wks post-initial treatment. Killed microfilaria by 12 wks
Moxi-doxy
- Advantage multi monthly for 10 mts
- Doxycycline BID for 30 days
- Efficacy 95.9% elimination of adult heartworms
- Killed microfilaria by 21 days
- *Corticosteroids recommended to suppress the inflammatory response of host
- *Tx of Wolbachia appears to mitigate this concern
Adulticidal treatment is expensive, best to do preventative. 90+ days, FDA 2 injections, Original slow kill, New slow kill, Moxi-doxy looks promising.
