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Whodunit, the cat or the dog?

27/10/2015

 
​The patient was a 12 year old girl who was originally from Eastern Europe having moved to the UK 5 years earlier. She presented to the paediatricians having become blind in one eye. The paediatricians and ophthalmologists could see a white lesion on fundoscopy and a provisional diagnosis of retinoblastoma was made. Blood tests were performed and the astute Paediatric Registrar who looked at the results noted that the patient’s eosinophil count was raised, and in fact this was the only abnormal result. The Paediatrician called the Microbiologist to ask if this might actually be infection instead of cancer.
 
There are a number of infections that can result in unilateral blindness including the more common infections like uveitis, keratitis and endophthalmitis as well as those that are less common e.g. Cytomegalovirus, toxoplasmosis and toxocariasis. Only one of these presents with a white lesion in the eye combined with a raised eosinophil count (eosinophilia), toxocariasis. On further questioning it was noted that whilst growing up in Eastern Europe the patient used to play outside where numerous stray dogs were present. Urgent blood samples were arranged for Toxocara spp. antibodies (both cat and dog!).
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What is toxocariasis?
Toxocariasis is an infection caused by Toxocara spp. which are roundworms that normally live in the guts of dogs (Toxocara canis) and cats (Toxocara catis). Humans are infected after eating the eggs excreted into the environment in dog and cat faeces. Toxocariasis is a zoonotic infection. Toxocariasis occurs all over the world and it is estimated that 10-15% of people have been exposed in Europe and North America, although this may be higher in tropical countries where the warmer temperatures are more favourable to the development of Toxocara spp. larvae.
 
Toxocara spp. in dogs and cats
Dogs and cats are the natural host for Toxocara spp. where the roundworm can undergo its full life cycle. Having been shed into the environment in the stool of infected animals the eggs take about three weeks to embryonate and become infective. Once eaten by another dog or cat the eggs hatch and the larvae penetrate through the intestinal wall into the lymphatics where they migrate to the lungs. The larvae enter the bronchial tree where they are coughed up and then swallowed. During this process the worms mature so that when they re-enter the small intestine they start to secret more eggs and the cycle of infection can occur again. Eventually larvae in the body become encysted and the infection becomes latent.
 
Another way that dogs and cats can become infected is by vertical transmission when encysted larvae reactivate during pregnancy and the puppy or kitten is then infected transplacentally. The final way in which dogs and cats can become infected is if they eat encysted larvae in the flesh of another animal which has become an accidental host to the worms e.g. a rabbit.
 
Toxocara spp. in humans
Humans are not a definitive host for Toxocara spp. and the worms are unable to complete their life cycle. As a result the larvae migrate to a variety of “abnormal” tissues e.g. heart, liver, brain, lungs, muscle and eyes, where they become encysted and trigger a local inflammatory response. It is this local inflammatory response that causes the symptoms and signs of toxocariasis in humans and the development of local granulomas.
 
How does toxocariasis present?
Toxocariasis is usually mild or asymptomatic infection, although a number of non-specific symptoms and signs can also occur e.g. fever, headache, altered behaviour, abdominal pain, hepatomegaly, rash, nausea and vomiting as well as wheeze and an asthma-like illness. There are two classical forms of toxocariasis, ocular larva migrans and visceral larva migrans both of which can cause long-term damage to the patient.
 
Ocular larva migrans (OLM)
OLM is more common in children than adults, and can present up to 10 years after the initial ingestion of the Toxocara spp. eggs. Symptoms are due to the development of granulomas in the eye causing unilateral visual disturbance and the presence of white granulomatous lesions which can be seen during fundoscopy. It is difficult to distinguish initially from the serious childhood cancer retinoblastoma. Untreated the infection can lead to retinal detachment and permanent blindness however, if treatment is started in time vision usually returns to normal (see treatment below).
 
Visceral larva migrans (VLM)
The symptoms of VLM are due to the larvae infecting various tissues in the body causing hepatitis, pneumonitis, fever, malaise, anorexia, skin rashes and a raised eosinophil count. VLM can mimic metastatic cancer with multiple pulmonary or hepatic nodules but the presence of an eosinophilia should suggest a possible parasitic cause. Despite the patient looking like they have end-stage cancer death is actually very rare, especially with treatment (see treatment below).
 
How is toxocariasis diagnosed?
The principal investigation for toxocariasis is the detection of Toxocara IgG in serum using a two-stage method of a highly sensitive but cheap enzyme-linked immunosorbent assay (ELISA) followed by a more specific and expensive western blot test (honest it is called this!). IgG remains positive after treatment or self-limited disease (although it does decrease a little) so a positive test in the absence of clinical symptoms or signs does not help to differentiate active from past infection and at present there is no test which can reliably do this.
 
Another way in which toxocariasis can be diagnosed is microscopically. The presence of larvae in infected tissue is diagnostic. Although biopsy is rarely indicated it is sometimes performed to rule out more serious pathology such as retinoblastoma unfortunately sometimes the diagnosis is made after eye surgery, whereas treatment could be curative before. Urgent blood samples for Toxocara spp. antibodies should be considered in all retinoblastoma patients before surgery. This is a reference laboratory test with results available in approximately 1 week.
 
How is toxocariasis treated?
For mild infections treatment is not usually required and the infection tends to be self-limiting over a period of a few weeks. OLM and VLM should be treated to prevent long-term damage to tissues.
 
OLM is treated with steroids e.g. prednisolone 0.5-1mg/kg/day to damp down the inflammatory response PLUS PO Albendazole (400mg OD children, 800mg OD adults) for 2-4 weeks. Surgery is only very rarely indicated to remove the granuloma and protect long-term vision.
 
VLM is treated with PO Albendazole 400mg BD for 5 days. YES this is less than the eye treatment regimen but this is because it is very difficult to get antimicrobials into the eye. If the patient has severe lung, heart or brain involvement then steroids may be indicated to help control the inflammation until the Albendazole has time to work.
 
Response to treatment should be assessed by monitoring the blood eosinophil count which should return to normal within a month of starting treatment.
 
So the young girl who had been sent to the Paediatricians with a possible diagnosis of retinoblastoma was treated with 4 weeks of Albendazole for toxocariasis, her eosinophil count returned to normal, and the lesion in her eye resolved without the need for any surgery. Her vision returned to normal. The Paediatrician made a stunning diagnosis, all were relieved that this wasn’t retinoblastoma. It is assumed that the patient acquired Toxocara canis from the stray dogs whilst living in Eastern Europe, although we will never know for certain…the cats however in this case were off the hook.
 
Great nerdy question for my fellow lab-rats out there: which “compass point” is not a blot test?!

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    Blog Author:

    David Garner
    Consultant Microbiologist
    Surrey, UK

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