Amebic Meningoencephalitis 

Updated: Oct 12, 2021
Author: Linda Nguyen, MD; Chief Editor: Russell W Steele, MD 


Practice Essentials

Amebic meningoencephalitis is an extremely rare and sporadic central nervous system (CNS) infection caused by free-living amoebae, mostly found in freshwater lakes and rivers. The initial symptoms of primary amebic meningoencephalitis (PAM) are indistinguishable from bacterial meningitis, while the symptoms of granulomatous amebic meningoencephalitis (GAE) can mimic a brain abscess or meningitis. Diagnosis can be made by observing motile amebae in a wet mount of cerebrospinal fluid (CSF) or visualization on CSF Wright or Giemsa stain. Treatment consists of a combination of systemic and intrathecal antibiotics.[1]


The free living amoebae that have been identified as CNS pathogens include Naegleria fowleri,[2] Paravahlkampfia francinae,[3]  Balamuthia mandrillaris,[4] and species of Acanthamoeba and Sappinia. (See Etiology.)[5]   Fulminant, acute presentations mimicking bacterial or viral meningoencephalitis are typically caused by N fowleri.  More subacute to chronic presentations mimicking aseptic meningitis, brain abscess, or CNS malignancy are more typical of the remaining species.


PAM can occur in previously healthy young individuals exposed to warm, especially stagnant, fresh water. The portal of entry by the amoebae is through the olfactory mucosa and the cribriform plate.[6] The pathophysiology is thought to be due to an amplified host immune response. This immune response traverses the blood brain barrier, causing an inflammatory reaction and subsequent parenchymal damage. It is thought that N. Fowleri causes an acute inflammatory cytokine response, whereas Acanthamoeba and Balamuthia spp. cause a type IV hypersensitivity reaction. These inflammatory responses contribute to neuronal damage and subsequent irreversible brain damage.[7]


Primary meningoencephalitis

Ubiquitous in most soils in most environments, N fowleri is also found in warm freshwater, particularly if the water is stagnant.[8] Exposure to the this amoeba is very common. Children younger than 2 years frequently carry the organism asymptomatically in their nose and throat, especially in warmer months and climates.  Infection with this pathogen occurs in both immunocompromised and immunocompetent individuals.[9]

PAM is an exceptionally uncommon occurrence resulting from CNS invasion of the typically healthy host by N fowleri. During a period of a few days to 2 weeks after inoculating a patient who had been swimming, diving, bathing, or playing in warm, usually stagnant, freshwater, the amoebae migrate through the cribriform plate, along the fila olfactoria and blood vessels, and into the anterior cerebral fossae, where they cause extensive inflammation, necrosis, and hemorrhage in the brain parenchyma and meninges.[10]  

Case reports have detailed rare infection following ritual ablution with tap water instilled into the nostrils.[11, 12] Similarly, sinus irrigation with contaminated tap (or other) water using neti pots (or similar devices) has been implicated as the mode of inoculation resulting in PAM.[13]

Granulomatous amebic encephalitis

In contrast to PAM, GAE results from one of two pathways.  With acanthamebic keratoconjunctivitis, amoebae may spread directly from the cornea to the CNS, though this is uncommon. More typically, GAE results from hematogenous seeding of the CNS following primary inoculation of the lungs or skin by B mandrillaris, Acanthamoeba, or Sappinia species.  Once in the CNS, the pathogen stimulates abscess and focal granuloma formation. GAE more commonly occurs in immunocompromised hosts; however, GAE may also affect otherwise healthy hosts.


Occurrence in the United States

PAM and GAE are extremely rare, with an average of 3.7 cases reported per year in the past 10 years.[14] From 1962-2015, 138 cases of PAM have been reported. Cases have been reported from 13 states (AZ, AR, CA, FL, IN, KS, LA, MN, OK, SC, TX, VA, and USVI).[1] PAM is more common in warmer regions and in the warmer months of spring and summer.[15]  Between 2010 and 2020, most cases in the United States (approximately 17) occurred in Texas and Florida.[16]

There is no seasonal variation with GAE. Approximately 60 cases of Balamuthia GAE have been reported in the US since 1975.[17] Sappinia, on the other hand, has only been documented as the pathogen responsible for a single case of GAE.[5]  

International occurrence

Although rare, cases of PAM and GAE have been reported worldwide, reflecting the ubiquity of the organisms.[18] More than 125 cases of Balamuthia GAE have been reported worldwide since 1975.[17] Most reports come from the United States, Australia, and Europe, although this is likely because of identification and reporting bias. Balamuthia infection in South America has been increasingly recognized.[19] Similar to the US experience, the predominance of PAM cases occurs in warmer climates and during warmer months of the year. 

Sex- and age-related demographics

The male-to-female ratio of PAM is 2:1 overall, but in the US there is a female predominance (63% of reported cases). PAM has been reported in infants as young as 4 months and is most commonly observed in the first 3 decades of life, with one study finding the median age of infection was 11 years (range: 4-56 years).[1]

The male-to-female ratio of GAE is 5:1 worldwide and can be seen at any age.


These infections are nearly uniformly fatal. The mortality rate remains greater than 90%, even with combination antimicrobial therapy.[20] The high mortality rate is likely because of delayed diagnosis and poor response to therapy. In most cases, the diagnosis is made postmortem.

Linam et al presented a survivor of amebic meningoencephalitis in North America. The authors conclude that the patient's survival most likely resulted from a variety of factors, including early identification and treatment, use of a combination of antimicrobial agents that included miltefosine, and management of elevated intracranial pressure based on the principles of traumatic brain injury. This was also the first case reported in which induced hypothermia to 32-34 degrees Celsius was used in the management of PAM.[21]


Reported complications are fatality, permanent brain damage, seizures, and comas.

Patient Education

For patient education resources, see the Brain and Nervous System Center, as well as Brain Infection.




The history seldom helps to differentiate amebic meningoencephalitis from other CNS diseases.

Primary amebic meningoencephalitis

 Characteristics of PAM are as follows:

  • PAM commonly affects children and young adults who have previously been healthy

  • This disease occurs more often during the warmer months of the year and in warmer climates

  • Patients with PAM typically have a history of swimming, diving, bathing, or playing in warm, generally stagnant, freshwater during the previous 1-9 days

  • Rarely, patients with PAM may experience disordered smell or taste

  • Most often, the symptoms of PAM are indistinguishable from those of acute bacterial meningitis.

  • The acute onset of PAM occurs over a period of hours to 1-2 days

Granulomatous amebic encephalitis

 The characteristics of GAE include the following:

  • It affects individuals of all ages, although those at the extremes of age may be more susceptible

  • Persons with debility or immunocompromise may be more susceptible to GAE

  • There is no seasonal variation because the causative pathogens are ubiquitous

  • Individuals with GAE may have keratoconjunctivitis or a skin ulcer or lesion preceding neurologic symptoms

  • A subacute or chronic presentation lasting days or weeks

General Presentation

The presentation of primary amebic meningoencephalitis closely mimics that of bacterial meningitis. Patients typically present with fever, headache, nausea, vomiting, photophobia, and stiff neck.[22] Additional symptoms include confusion, somnolence, seizures, and coma. In all cases reported to date, there has been a history of water entry into the nose.[23] Symptom onset begins 1-9 days after such an exposure.[24]

Typical symptoms of GAE include low-grade fever and focal neurologic signs, such as cranial nerve palsies, hemiplegia, ataxia, aphasia, diplopia, and seizures. Patients with GAE may also exhibit behavioral changes, stiff neck, signs of increasing intracranial pressure (ICP), stupor, or coma. Symptom onset ranges from weeks to months after exposure. Interestingly, cases of Balamuthia have been reported with patients’ skin lesions occurring months to years prior to the onset of neurologic manifestations.[25]

Physical Examination

Physical examination seldom helps to differentiate amebic meningoencephalitis from other CNS diseases.

Primary amebic meningoencephalitis

Patients may uncommonly experience abnormal smell or taste. Typical signs include high fever, photophobia, stiff neck, mental status change, and seizures. PAM may progress rapidly to cerebral herniation secondary to increased intracranial pressure. Rarely, myocarditis may occur, although amoebae are not present in the myocardium on histologic evaluation.

Granulomatous amebic encephalitis

Individuals with GAE may have low-grade fever, photophobia, and/or stiff neck. Focal neurologic findings, such as cranial nerve palsies, hemiplegias, aphasias, ataxias, or diplopia, are observed more commonly. When present, seizures may be focal or generalized. Later in the disease course, GAE patients may demonstrate signs of elevated ICP and cerebral herniation. Keratoconjunctivitis, primarily in people who wear contact lenses, or skin lesions may rarely predate neurologic signs and symptoms.





Approach Considerations

Lumbar puncture for cerebral spinal fluid (CSF) analysis is the primary diagnostic tool for PAM, whereas tissue diagnosis is essential for GAE. Nonetheless, amebic meningoencephalitis is seldom diagnosed prior to autopsy. Difficulties in diagnosis and rapid progression make this condition extremely difficult to treat effectively. For this reason, aggressively pursue the diagnosis in patients with CSF findings consistent with bacterial meningitis, a negative CSF gram stain, and a history of water exposure.

CSF findings differ somewhat between patients with PAM and those with GAE. CSF analysis in GAE typically demonstrates less inflammation than in PAM. In addition, trophozoites may be present in the CSF of patients with PAM but are not observed in the CSF of patients with GAE. Histopathologic examination of tissue biopsies has a higher yield for detecting GAE pathogens.

CSF Analysis

Primary amebic meningoencephalitis

As previously mentioned, lumbar puncture for CSF analysis is the primary diagnostic tool for PAM. CSF analysis is indistinguishable from that of acute bacterial meningitis, except that Gram stain findings are always negative. Opening pressure is high (median of 385 mmH2O), red blood cells are elevated (median of 265 cells/uL), white blood cell count is high (median of 2,400 cells/uL; predominantly neutrophils), protein is high (median of 365 mg/dL), and glucose is low (median of 23 mg/dL).[24]

If PAM is suspected, light microscopy with phase contrast on fresh, still-warm CSF may reveal motile trophozoites. Clinicians should also consider a cell culture assay, which will demonstrate cytotoxicity within 48 hours of inoculation in the presence of N fowleri.

A triplex real-time polymerase chain reaction (PCR) assay for N. fowleri, Acanthamoeba spp, and B. mandrillaris has been developed by the Centers for Disease Control and Prevention (CDC).[26] Multiplex PCR for the above and for Sappinia species is likely to become available in the near future.[27]

Granulomatous amebic encephalitis

As with PAM, lumbar puncture for CSF analysis is the first step in diagnosing GAE. CSF analysis typically demonstrates less inflammation than that observed in PAM, and trophozoites are typically not seen in the CSF. Opening pressure is elevated. Similar to aseptic meningitis, a lymphocytic pleocytosis (typically fewer than 500 cells/mm3) is seen. There may be elevated protein levels (up to 1000 mg/dL) early in the clinical course. Often, near-normal or slightly decreased glucose levels are seen.

Imaging Studies

Head computed tomography (CT) scanning or magnetic resonance imaging (MRI) should precede lumbar puncture if clinical signs of focal CNS involvement or elevated intracranial pressure (ICP) is present. In PAM, CT scan or MRI shows obliteration of the cisterns surrounding the midbrain and subarachnoid space, which are nonspecific findings.[28]

In individuals with GAE, focal lesions are very common and may be found scattered throughout the CNS.[29] CT and MRI of the brain typically show multifocal low-density lesions in both cortical and subcortical regions. Enhanced CT may show progressive hydrocephalus, meningeal thickening, pseudotumoral lesions, large isolated lesions, or multifocal ring-enhancing lesions. MRI may demonstrate multifocal lesions, edema, and multiple ring-enhancing lesions.[28] However, given these nonspecific findings, neuroimaging only has the potential for suggesting the diagnosis of PAM or GAE amidst a range of other possible etiologies and is never diagnostic.

Other Tests

For GAE, the conventional method used is histologic detection of the trophozoite and cyst forms of the parasite in biopsied tissue. Biopsy sites may include skin, sinus, lung, and brain tissue.

In PAM, N. fowleri serology is not clinically useful given the rapid progression of disease. However, in GAE, the subacute or chronic progression allows for the potential of serologic testing to be of diagnostic value. Various methods, such as indirect immunofluorescence, ELISA, and flow cytometry may be used to detect antibodies.[17]

Histologic Findings

Biopsies and postmortem specimens from persons with PAM reveal severe, suppurative meningoencephalitic changes and necrotic brain tissue within which amebic trophozoites and macrophages are visualized.[30, 31]

A biopsy of focal granulomatous lesions in GAE is essential for diagnosis. Moderate granulomatous inflammation with prominent vascular involvement is typically present on brain biopsy. Multiple hemorrhagic and necrotic lesions can be found in the cerebrum, thalamus, midbrain, pons, medulla, and cerebellum.  Liquefactive necrosis, marked edema, hemorrhage, and necrotizing vasculitis are associated with the accumulation of amoebic trophozoites, amoebic cysts, and inflammatory cells.[32, 33]

Immunohistochemistry has been widely used to detect the amoebae in histologic specimens. Immunofluorescent antibodies targeting amebic antigens are added to biopsied tissue to differentiate tissue macrophages and necrosed keratinocytes from amoebae.[3]

Tissue-based polymerase chain reaction (PCR) assay has been proposed as a diagnostic aid in patients infected with free-living amoebae, but is not commercially available.[26]



Approach Considerations

Admit patients with amebic meningoencephalitis to the intensive care unit (ICU) for intensive monitoring and therapy. Arrange transfer if appropriate specialists and resources are otherwise unavailable.

Typically, PAM rapidly progresses, appearing like an overwhelming acute bacterial meningitis unresponsive to routine antibacterial agents.


Measures to prevent PAM and GAE include the following:

  • The clinician should routinely discuss with individuals the risks of exposure to free-living amoebae in warm, typically stagnant, freshwater

  • Some have advocated the avoidance of diving and jumping into these waters

  • Advise individuals to consider the use of nose plugs for unavoidable exposures

  • Advise individuals to verify adequate chlorination of swimming pools

  • Since Acanthamoeba can cause keratitis, contact lens wearers should be advised to visit their provider for regular eye exams, replace contacts as prescribed, remove lenses before activity involving contact with water, wash hands with soap before handling contact lenses, and clean lenses as instructed by manufacturer

  • Immunocompromised patients are more susceptible to developing these infections, however, there are no additional preventive measures for this population


Emergent consultations with infectious disease specialists, neurologists, and neurosurgeons are recommended if PAM or GAE is suspected. There is 24/7 diagnostic assistance, specimen collection guidance with shipping instructions, and treatment recommendations offered by the CDC Emergency Operations Center at 770-488-7100. The CDC also offers an investigational drug called Miltefosine for free-living ameba infections caused by N. fowleri, B. mandrillaris, and Acanthamoeba species.

Medical Care

In both PAM and GAE, the mortality rate is approximated at 95%, and all survivors have received combination amoebicidal therapy.  Because of the low incidence of these infections and the high mortality rate, there have been no clinical trials to date defining optimal therapy. CDC recommendations are based on data accumulated from published case reports and in vitro data.

Primary amebic meningoencephalitis

The cornerstone of PAM treatment is amphotericin B deoxycholate (AMB), at maximally tolerated doses, plus miltefosine with adjunctive therapy. The CDC currently recommends the following multidrug regimen:

  • Amphotericin B 1.5 mg/kg/day intravenous (IV) in 2 divided doses for 3 days, then 1 mg/kg/day for 11 days

  • Amphotericin B 1.5 mg intrathecal daily for 2 days, then 1 mg/day every 48 hours for the next 8 days

  • Azithromycin 10 mg/kg/day IV/oral (PO) for 28 days

  • Fluconazole 10mg/kg/day IV/PO for 28 days

  • Rifampin 10 mg/kg/day IV/PO for 28 days

  • Miltefosine 50 mg bid (if weight is less than 45 kg) and 50mg tid (if weight is more than 45 kg) PO for 28 days

  • Dexamethasone 0.6 mg/kg/day IV in 4 divided doses for 4 days

In vitro studies and mouse models have indicated that miltefosine, chlorpromazine, and rokitamycin may have activity against PAM. Miltefosine in particular has been used in 2 of the 5 known cases to have survived.  In the first, the treatment regimen, which included miltefosine as well as induced hypothermia, there was complete neurologic recovery (32-34C).[21] The second patient, also treated with miltefosine but without induced hypothermia, survived with permanent brain damage.[34] Thus, the CDC recommends miltefosine as well as amphotericin B deoxycholate as the backbone of any treatment regimen.

Of note, although liposomal formulations of AMB tend to be preferred for other types of CNS infections, the conventional formulation, amphotericin B deoxycholate, is the preferred formulation for PAM and GAE. In vitro data indicates that for N. fowleri, the minimum inhibitory concentration (MIC) for conventional AMB was 0.1 ug/mL compared to an MIC of 1 ug/mL for liposomal AMB.

Steroids, which have a protective role against short-term neurologic sequelae, mortality, and severe hearing loss in patients with bacterial meningitis, are recommended for PAM for the same theoretical benefits.

Granulomatous amebic encephalitis

There has been success with several combination treatment regimens:


  • Several cases: Pentamidine +Sulfadiazine + Flucytosine + Fluconazole or Itraconazole

  • AIDS: Sulfadiazine + Pyrimethamine + Fluconazole + surgical resection of CNS lesion

  • Chronic Acanthamoeba meningitis: Trimethoprim/Sulfamethoxazole + Rifampin + Ketoconazole

  • Disseminated cutaneous infection: IV Pentamidine + topical Chlorhexidine + 2% Ketoconazole cream, followed by PO Itraconazole + Voriconazole + Amphotericin B lipid complex

Balamuthia mandrillaris

  • Two cases: Flucytosine + Pentamidine + Fluconazole + Sulfadiazine + Azithromycin or Clarithromycin + surgical resection of CNS lesion

  • One case: Pentamidine + Fluconazole + Sulfadiazine + Clarithromycin

Sappinia diploidea (1 case)

  • Azithromycin + Pentamidine + Itraconazole + flucytosine + surgical resection of CNS lesion

In conjunction with the FDA, the CDC has an expanded access investigational new drug (IND) protocol in effect to make miltefosine, an amebicidal agent, available directly from the CDC for treatment of free-living amebae (FLA) in the United States. These infections include primary amebic meningoencephalitis (PAM) caused by N. fowleri and granulomatous amebic encephalitis caused by B. mandrillaris and Acanthamoeba species.[35]

Surgical Care

Primary amebic meningoencephalitis

PAM may require the placement of a reservoir for intrathecal amphotericin B or miconazole. Hydrocephalus may necessitate shunting.

Granulomatous amebic encephalitis

Brain biopsy is essential for diagnosis. Excision of solitary or isolated lesions may be of clinical benefit. Retrospective analysis of survival cases show a combination of surgical management and antibiotic therapy.[36] Hydrocephalus may necessitate shunting.



Medication Summary

Amphotericin B is the drug of choice (DOC) in the treatment of PAM, and should always be used in combination with at least one amebicidal drug. Amphotericin B and/or ketoconazole are among the drugs administered to patients with GAE. Miltefosine is an investigational amebicidal drug provided by the CDC for adjunctive treatment of PAM and GAE.

Antifungals, Systemic

Class Summary

Various antifungal agents with amebistatic properties are used in combination and at maximal doses, both parenterally and intrathecally. One case report suggested that oral combination therapy for Acanthamoeba meningitis may be successful, but this result has not been reproduced. Azole drugs have been found to have amebicidal properties and are used as adjunctive therapy for both PAM and GAE.

Amphotericin B deoxycholate (Amphotericin B (conventional), Fungizone)

Amphotericin B is amebistatic at low levels. It is the basis of therapy for all PAM survivors and is also used for GAE. This agent remains the DOC for both conditions in the absence of further studies.. Amphotericin B is a polyene antibiotic with poor oral bioavailability. It is produced by a strain of Streptomyces nodosus.   The minimum inhibitory concentration for conventional AMB was 0.1 ug/mL, while liposomal AMB was 10x higher at 1 ug/mL for N. fowleri. Amphotericin B has been shown to be amebistatic as demonstrated by drug efficacy tests.

Amphotericin B, lipid-complex (Abelcet)

Amphotericin B lipid complex consists of amphotericin B complexed with two phospholipids in a 1:1 drug-to-lipid- molar ratio. Among the 3 lipid formulations of amphotericin B, no data regarding their therapeutic efficacy, safety, or dosing for PAM or GAE are available. They have been used with disseminated cutaneous infection.   

Amphotericin B, liposomal (AmBisome)

This is a lipid preparation consisting of amphotericin B within unilamellar liposomes. It delivers higher concentrations of the drug, with a theoretical increase in therapeutic potential and decreased nephrotoxicity.

Amphotericin B is a polyene antibiotic with poor oral availability. It is produced by a strain of Streptomyces nodosus, and it can be fungistatic or fungicidal. The drug binds to sterols (eg, ergosterol) in the fungal cell membrane, causing leakage of intracellular components and fungal cell death. Toxicity to human cells may occur via this same mechanism.

Amphotericin B colloidal dispersion (Amphotec)

Amphotericin B colloidal dispersion is a lipid preparation consisting of amphotericin B attached to lipid discoid structures. Amphotericin B is a polyene antibiotic with poor oral availability. It is produced by a strain of Streptomyces nodosus, and it can be fungistatic or fungicidal. The drug binds to sterols (eg, ergosterol) in the fungal cell membrane, causing leakage of intracellular components and fungal cell death. Toxicity to human cells may occur via this same mechanism.

Rifampin (Rifadin IV)

Rifampin has amebicidal activity in vitro and is synergistic with amphotericin B when administered intravenously. It inhibits ribonucleic acid (RNA) synthesis in bacteria by binding to the beta subunit of deoxyribonucleic acid (DNA) ̶ dependent RNA polymerase, which, in turn, blocks RNA transcription.

Doxycycline (Vibramycin, Doxy 100, Doryx, Adoxa)

Doxycycline has amebicidal activity in vitro and is synergistic with amphotericin B when administered intravenously. It inhibits protein synthesis and, consequently, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Erythromycin ethylsuccinate-sulfisoxazole (E.S.P.)

The combination of erythromycin and sulfisoxazole is well absorbed from the gastrointestinal (GI) tract but is best administered on a full stomach to avoid GI upset. Erythromycin inhibits bacterial protein synthesis. Sulfisoxazole inhibits the synthesis of folic acid from para-aminobenzoic acid in bacteria.


Ketoconazole is an amebicidal imidazole that, in combination with amphotericin B, is the DOC for GAE. It inhibits the synthesis of ergosterol, allowing cellular components to leak and, consequently, causing fungal cell death to occur.


Sulfadiazine has amebicidal activity in vitro and is synergistic with ketoconazole and/or amphotericin B. It exerts bacteriostatic action by competitive antagonism of PABA.

Azithromycin (Zithromax, Zmax)

Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms and blocking the dissociation of peptidyl transfer RNA (tRNA) from ribosomes; this causes RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected. Azithromycin also has known immunomodulatory properties that may confer additional anti-inflammatory benefits.

Azithromycin concentrates in phagocytes and fibroblasts, as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues. Azithromycin treats mild to moderate microbial infections. It may have an adjunctive role with amphotericin B in the treatment of GAE/PAM.

Flucytosine (5-FC, 5-fluorocytosine, Ancobon)

Flucytosine is taken up by fungal cells and is converted into 5-fluorouracil (5-FU), which is then converted to metabolites that inhibit fungal RNA and DNA synthesis. Flucytosine has been shown to be effective in the amoebae causing GAE in vitro and can be used as adjunctive therapy for GAE.

Trimethoprim/sulfamethoxazole (Bactrim, Bactrim DS, Cotrim)

The combination drug has synergy in inhibiting the folate synthesis pathway. Trimethoprim inhibits the dihydrofolate reductase step and sulfamethoxazole inhibits the dihydropteroate synthetase step. This drug works de novo on microbial organisms, including amoebae, and has been used in GAE treatment.

Antiparasitic Agents

Pyrimethamine (Daraprim)

Pyrimethamine inhibits folic acid synthesis by inhibiting dihydrofolate reductase and therefore inhibits DNA and RNA synthesis. This drug is effective in many species, including amoebae, and has been used adjunctively in GAE.

Antipneumocystis Agents

Pentamidine (NebuPent, Pentam)

The mechanism of Pentamidine is unknown but likely involves the mitochondria. It has been used as adjunctive therapy to treat GAE.

Antileishmaniasis Agents

Miltefosine (Impavido)

Miltefosine likely interacts with lipids, including those on cell membranes, inhibits cytochrome c oxidase in mitochondrial function, and leads to cellular apoptosis. Initially studied as a chemotherapeutic agent to treat breast cancer, it was found to be an effective anti-amebic drug. The CDC now offers Miltefosine as an investigational drug in the treatment of PAM and GAE.