Acanthamoeba and Balamuthia

There are many free-living amoeba, but only four have been causally associated with disease in humans. These are Acanthamoeba spp., Balamuthia mandrillaris (only known species of Balamuthia), Naegleria fowleri and Sappinia diploidea. The family Acanthamoebidae consists of the two genus' called Acanthamoeba and Balamuthia, which will be discussed in this article.¹ These organisms live as parasites when they invade humans and animals.

The amoeba belonging to the genus' Acanthamoeba and B. mandrillaris can lead to various illnesses in humans. Examples are as follows (there is a predilection in immunocompromised or debilitated hosts):^1,2

• Granulomatous amoebic encephalitis (GAE) - caused both by Acanthamoeba and Balamuthia
• Amoebic keratitis (AK) - caused by Acanthamoeba spp.
• Other species of the Acanthamoeba can cause illness in immunocompromised hosts e.g. skin lesions or sinusitis

These organisms are ubiquitous and found worldwide. They are found in soil, dust, air and water (e.g. swimming pools, domestic and sewage). They have also been isolated in hospitals, contact lenses and cell cultures. In cell cultures they are commonly contaminants. In fact, this is how they were discovered in the 1950's - they grew on cell cultures grown for the polio vaccine. Acanthamoeba can also be found in fish and has been isolated from the nasal and throat mucosa of healthy humans.

Both Acanthamoeba and Balamuthia can act as hosts for other bacterial infections, e.g. legionella. Further research into this area is ongoing.^2,3

There are 2 stages:^1,2

1. Active feeding stage:
   • During this stage the trophozoites are actively dividing by feeding on bacteria, yeast and algae or axenically (i.e. not associated with any other organisms).
2. Dormant cyst stage:
   • Cysts form once there is a change in the environment of the trophozoites e.g. nutrient deprivation or changes in temperature. The cysts are resistant to chlorination and antibiotics.

Caused by both Acanthamoeba spp. and Balamuthia.

• Description - chronic, slowly progressive infection of the CNS. May involve lungs also.
• Causative organism - several Acanthamoeba spp. and Balamuthia spp. may cause GAE.
• Incubation period - unknown but estimated at weeks to months. Route of infection is aerosol or direct inoculation with haematogenous spread to the CNS.
• Epidemiology - GAE is a very rare cause of disease and most publications are case reports.¹ Most cases are not identified until post-mortem due to the lack of good and reliable diagnostic tests and secondary infections being more common.
  Commonly seen in immunocompromised patients, including those with neoplasia, systemic lupus erythematosus, human immunodeficiency virus and tuberculosis. However, cases have been seen in the immunocompetent, for example, Balamuthia infections in children.⁴
• Risk factors - alcoholism, drug abuse, chemotherapy, corticosteroids and organ transplantation.
• Presentation:
  • Symptoms - headache, confusion, fever, lethargy, nausea and vomiting, seizures, photophobia and neck stiffness. Patients may become frankly psychotic.
  • Signs - neck stiffness and focal neurological deficits. The latter include the following: hemiparesis, cranial nerve deficits (e.g. facial nerve palsy), diplopia, ataxia and positive babinski sign and positive Kernig's sign. Patients may also develop raised intracranial pressure.
• Diagnosis - cerebrospinal fluid smear (usually lymphocyte predominance and low glucose), culture, immunofluorescence or polymerase chain reaction (PCR).⁵ In AIDS patients the CSF may be lacking in cells making diagnosis difficult. Brain biopsy may be required. CNS imaging e.g. CT and MRI may reveal enhancing or non-enhancing lesions and is thus non-diagnostic. Balamuthia does not grow on agar plates, unlike Acanthamoeba. However, similar to Acanthamoeba, Balamuthia is difficult to isolate from CSF specimens.²
• AIDS patients - may have disseminated infection. They may also have chronic sinusitis, otitis and skin lesions. Cases of vasculitis and osteomyelitis have also been reported.
• Differential diagnosis - bacterial or viral meningitis, toxoplasmosis or CNS vasculitis (last two in AIDS patients).
• Prognosis - mortality is high with GAE, reaching almost 100% when both skin lesions and CNS disease occur together.
• Treatment - GAE is treated with pentamidine usually in combination with one or more of the following: ketoconazole, hydroxystilbamidine, paromomycin, 5-fluorocytosine polymyxin, sulfadiazine, trimethoprim-sulfamethoxazole and azithromycin. Similar medications are used in the treatment of Balamuthia.²

Caused by both Acanthamoeba spp. and Balamuthia spp..

• Skin lesions - hard nodules or non-healing, indurated skin ulcers can occur.
• Treatment - skin lesions are difficult to treat and even harder when the CNS is also involved. Regimens including itraconazole, pentamidine, 5-flucytosine have been used. Topical chlorhexidine and ketoconazole are also used in addition to systemic therapies.
• Prognosis - 76% mortality is associated with skin disease alone (higher when GAE also present - see above).

• Description - progressive disease of the cornea which is sight-threatening
• Causative organism - several Acanthamoeba spp. may cause AK.
• Commonly seen in - immunocompetent patients. However, infection does not confer immunity and re-infection is common.
• Risk factors - poor contact lens hygiene, corneal abrasion or exposure of the eye to contaminated water.
• Epidemiology - the incidence of Amoebic keratitis (AK) is 3 per 100,000 and around 85% of cases occur in people who wear contact lenses. In a Scottish study the incidence amongst wearers of soft contact lenses was 14.9 per 100,000.⁶An epidemic of AK occurred in the USA in 1980s which was related to contaminated contact lenses and solutions.
• Presentation - secondary bacterial infection occurs commonly making it difficult to diagnose.
  • Symptoms - watering of eyes, eye pain with photophobia, blurred vision and irritation are common.
  • Signs - include ptosis, conjunctival hyperemia, episcleritis, scleritis and loosening of the corneal epithelium. Stromal infiltrates can be seen with a bright light. Rarely trophozoites can infiltrate the corneal nerve and retina leading to chorioretinitis.
• Diagnosis - corneal scrape or biopsy.
• Differential diagnosis - herpes keratitis or fungal keratitis.
• Treatment - wide epithelial debridement if infection detected early - but try to achieve medical resolution first.⁷ Therapy should include the cationic antiseptic agents, of which chlorhexidine or polyhexamethylene biguanide (PHMB) are the most effective. This is in combination with propamidine isethionate and neomycin as part of triple therapy. These may have to be used for prolonged periods e.g. more than a year. Imidazoles have also been used but success rates are not great. In severe cases enucleation may be necessary.
• Prevention - killing Acanthamoeba spp. from contact lens. Tap water should not be used to rinse contact lenses. Also see box below.