Time and aggressive multi-drug therapy is of the essence in this disease at this time. Miltefosine is now available through CDC for emergency use under an expanded access IND protocol.
For 24/7 diagnostic assistance, specimen collection guidance, shipping instructions, and treatment recommendations, please contact the CDC Emergency Operations Center at 770-488-7100:
Miltefosine is a drug used in cancers that has shown benefit in Naegleria in vitro, and is manufactured in Europe. CDC recently obtained approval from FDA for an expanded access investigational new drug (IND) protocol that will allow for release of miltefosine directly from stock stored at CDC headquarters in Atlanta, Georgia. Clinicians suspecting amoeba infection should contact CDC Emergency Operations Center at 770-488-7100 to consult with a free-living ameba expert.
In addition, other available treatments are still worth trying, especially if treatment can be initiated within 12-24 hours of symptom onset. Given that a prospective, randomized controlled clinical trial is unlikely in this highly lethal condition, clinicians will have to rely on aggressive best guesses, as the worst that could happen is already happening. I appeal to my clinician colleagues across the globe to publish the very valuable results of any attempted treatments, successful or unsuccessful, in the interest of adding to the sparse literature on this devastating parasitosis.
Drugs which have been used successfully include IV or intrathecal Amphotericin B, fluconazole, and rifampin. In a 2005 case, treatment of a child with corticosteroids and these antimicrobials was initiated 9 hours after headache onset, with full recovery. In animal models and in vitro, azithromycin, minocycline, and linezolid offer synergy with amphotericin B against Naegleria. Given the intermittent success of current treatments, some experts propose aggressive multi-drug and multi-site delivery approaches, as for cancer chemotherapies, including IV, intra-thecal, and intra-nasal deliveries. It would seem to make sense that more aggressive measures are warranted in as duration of symptoms approach the 48-72 hour mortality mark.
Useful details about performing intrathecal infusion of amphotericin B may be found in this reference, “Lumbar puncture drainage with intrathecal injection of amphotericin B for control of cryptococcal meningitis” ; contrary to popular belief, IT amphotericin B is well-tolerated with only mild nerve root irritation symptoms in some cases. Click the link to download the PDF of Cryptococcus Intrathecal Amphotericin Protocol.
The following abstracts are offered as informational resources, however, more literature may be found by searching literature search tools such as PubMed or Ovid.
Arch Med Res. 2005 Jan-Feb;36(1):83-6.
Successful treatment of Naegleria fowleri meningoencephalitis by using intravenous amphotericin B, fluconazole and rifampicin.
Department of Pediatrics, Hospital de Especialidades 1, Centro Medico Nacional Noroeste, Instituto Mexicano del Seguro Social, Ciudad Obregon, Sonora, Mexico.
Primary amebic meningoencephalitis (PAM) is an emerging disease with a rapidly fatal outcome. Only eight reports of cured cases have appeared in the medical literature to date.
A 10-year-old boy developed PAM caused by Naegleria fowleri 1 week after swimming in an irrigation canal. He was admitted to our hospital after 9 h of severe headache and vomiting, fever, ataxic gait, mild confusion, and seizures were evident. Trophozoites were identified in the cerebrospinal fluid (CSF). Treatment with intravenous (i.v.) dexamethasone, amphotericin B, fluconaloze, and oral rifampicin was started. After several hours of conflicting clinical signs, recovery began, and on the third day he was conscious again. Hospital discharge occurred on day 23, after a normal brain CT scan. There was no sequel to the disease during the following 12 months.
The amebas present in the CSF were identified and confirmed as N. fowleri after observation of wet mounts and of cultures seeded on 1.5% non-nutrient agar plates covered with Escherichia coli, vegetative and cystic forms, enflagellation experiments in distilled water at 98 degrees F, temperature tolerance testing and by indirect immunofluorescence using N. fowleri LEE antibody. The genotype was determined by PCR amplification and sequencing of the internal transcribed spacers (ITS) including the 5.8S rDNA.
Early treatment of PAM by i.v. administration of amphotericin B and fluconazole, and oral administration of rifampicin can offer some hope of cure for this devastating disease.
Med Hypotheses. 2008 Dec;71(6):969-71. doi: 10.1016/j.mehy.2008.06.037. Epub 2008 Aug 19.
[Click to download the full text PDF at this link, Naegleria and Multidrug Therapy.]
Survival of Naegleria fowleri primary amebic meningocephalitis (PAM) could be improved with an intensive multi-route chemo- and biotherapeutic regimen.
Marshfield Clinic Research Foundation, Marshfield, WI 54449, USA. Alisky.Joseph@marshfieldclinic.org
Naegleria fowleri primary amebic meningoencephalitis (PAM) has a very high mortality rate, probably exceeding 95%. A few people have survived after getting intravenous and intrathecal amphotericin, variably coupled with other agents that include dexamethasone, diflucan, chloramphenicol and rifampin, but even with prompt initiation of therapy, it is still a very uphill battle.
PRESENTATION OF THE HYPOTHESIS:
Survival could be improved by combined intrathecal, intranasal and intravenous amphotericin, diflucan and rifampin, with aduvant intravenous chloramphenicol, muramyl dipeptide, azithromycin, minocycline and linezolid, intramuscular trifluoperazine, intranasal Cry1C protoxin and intrathecal anti-Naegleria immune globulin and dexamethasone.
HYPOTHESIS RATIONALE: Instilling medications intranasally, intravenously and intrathecally would target the primary reservoir of infection and its common sites of spread. Intrathecal dexamethasone should attenuate cerebral edema, a primary cause of death in PAM. Azithromycin and minocycline appear to have synergy with amphotericin in killing N. fowleri in animal models, and the other agents, which also showed efficacy in animal models, should also be additive or synergistic as well. In essence one would approach PAM in the manner of chemotherapy for tuberculosis and cancer, with multidrug therapy to assure complete eradication.
TESTING THE HYPOTHESIS:
The hypothesis could be validated using murine and bovine models of N. fowleri PAM.
IMPLICATIONS OF THE HYPOTHESIS:
PAM may be emerging as a significant public health threat, underscoring the need for effective therapeutic regimens.