A pediatric case of primary amoebic meningoencephalitis due to Naegleria fowleri diagnosed by next-generation sequencing of cerebrospinal fluid and blood samples

Background Primary amoebic meningoencephalitis (PAM) is a rare, acute and fatal disease of the central nervous system caused by infection with Naegleria fowleri (Heggie, in Travel Med Infect Dis 8:201–6, 2010). Presently, the majority of reported cases in the literature have been diagnosed through pathogen detection pathogens in the cerebrospinal fluid (CSF). This report highlights the first case of pediatric PAM diagnosed with amoeba infiltration within CSF and bloodstream of an 8-year-old male child, validated through meta-genomic next-generation sequencing (mNGS). Case presentation An 8-year-old male child was admitted to hospital following 24 h of fever, headache and vomiting and rapidly entered into a coma. CSF examination was consistent with typical bacterial meningitis. However, since targeted treatment for this condition proved to be futile, the patient rapidly progressed to brain death. Finally, the patient was referred to our hospital where he was confirmed with brain death. CSF and blood samples were consequently analyzed through mNGS. N. fowleri was detected in both samples, although the sequence copy number in the blood was lower than for CSF. The pathogen diagnosis was further verified by PCR and Sanger sequencing. Conclusions This is the first reported case of pediatric PAM found in mainland China. The results indicate that N. fowleri may spread outside the central nervous system through a damaged blood–brain barrier.

Primary Amoebic Meningoencephalitis by Naegleria fowleri: Pathogenesis and Treatments

Naegleria fowleri is a free-living amoeba (FLA) that is commonly known as the “brain-eating amoeba.” This parasite can invade the central nervous system (CNS), causing an acute and fulminating infection known as primary amoebic meningoencephalitis (PAM). Even though PAM is characterized by low morbidity, it has shown a mortality rate of 98%, usually causing death in less than two weeks after the initial exposure. This review summarizes the most recent information about N. fowleri, its pathogenic molecular mechanisms, and the neuropathological processes implicated. Additionally, this review includes the main therapeutic strategies described in case reports and preclinical studies, including the possible use of immunomodulatory agents to decrease neurological damage.

A Fatal Case of Primary Amoebic Meningoencephalitis (PAM) Complicated with Diabetes Insipidus (DI): A Case Report and Review of the Literature

Naegleria fowleri is a highly infective free-living amoeba usually isolated from soil and fresh water and is primarily found to infect the central nervous system (CNS) resulting in primary amoebic meningoencephalitis (PAM). PAM as a cause of meningitis is often overlooked for other, more common causes of meningitis. Despite all the advances in antimicrobial therapy and supportive care systems, the mortality rate of this rare infection remains above 95% with the bulk of the cases being found in developed countries. We are presenting a case of a 44-year-old male with fever, worsening headache, and generalized weakness. Lumbar puncture showed a raised leucocyte count of 1100/µL with predominant polymorphonuclear cells, and wet mount prep for Naegleria fowleri was positive further confirmed with PCR. The patient was started Intravenous (IV) and intrathecal amphotericin-B, Per Oral (PO) miltefosine, IV rifampin, IV fluconazole, and IV dexamethasone. However, the patient started producing urine at 300–500 ml/hour. The patient’s sodium levels increased from 144 to 175 mmol/L in 12 hours with raised serum osmolality and decreased urine osmolality and urine sodium. The patient was started on PO desmopressin of 0.2 micrograms twice daily after which his urine output dropped to 60–80 ml/hour and sodium decreased from 175 to 162 and, later 155 mmol/L; however, the patient expired. PAM is a rare and extremely fatal illness, but with increasing incidence now being reported in developing countries as a result of better diagnostics. DI is a very rare complication reported in these patients leading to poor outcome. The complication of diabetes insipidus (DI) has not been extensively studied in patients having PAM. Only three cases have been reported with this complication. No mechanism has been mentioned in the literature behind the development of DI in these patients, and no study has mentioned laboratory details of DI as mentioned in this report.

Inhibition of Fatty Acid Oxidation as a New Target To Treat Primary Amoebic Meningoencephalitis

ABSTRACT Primary amoebic meningoencephalitis (PAM) is a rapidly fatal infection caused by the free-living amoeba Naegleria fowleri. The amoeba migrates along the olfactory nerve to the brain, resulting in seizures, coma, and, eventually, death. Previous research has shown that Naegleria gruberi, a close relative of N. fowleri, prefers lipids over glucose as an energy source. Therefore, we tested several already-approved inhibitors of fatty acid oxidation alongside the currently used drugs amphotericin B and miltefosine. Our data demonstrate that etomoxir, orlistat, perhexiline, thioridazine, and valproic acid inhibited growth of N. gruberi. We then tested these compounds on N. fowleri and found etomoxir, perhexiline, and thioridazine to be effective growth inhibitors. Hence, not only are lipids the preferred food source for N. gruberi, but also oxidation of fatty acids seems to be essential for growth of N. fowleri. Inhibition of fatty acid oxidation could result in new treatment options, as thioridazine inhibits N. fowleri growth in concentrations that can be reached at the site of infection. It could also potentiate currently used therapy, as checkerboard assays revealed synergy between miltefosine and etomoxir. Animal testing should be performed to confirm the added value of these inhibitors. Although the development of new drugs and randomized controlled trials for this rare disease are nearly impossible, inhibition of fatty acid oxidation seems a promising strategy as we showed effectivity of several drugs that are or have been in use and that thus could be repurposed to treat PAM in the future.

A Fatal Case of Primary Amoebic Meningoencephalitis from Recreational Waters

Background. Naegleria Fowleri is a single-cell, thermophilic amphizoid amoeba, and a rare known causative agent for primary amoebic meningoencephalitis with >97% mortality rate. The amoeba resides in freshwater lakes and ponds but can also survive in inadequately chlorinated pools and recreational waters. The mode of infection includes activities such as diving or jumping into freshwater or submerging the head under the water. Although most commonly seen in the southern United States, it is essential to keep this clinical suspicion in mind regardless of geography, as presenting symptoms can be very similar to classic bacterial meningitis. Case Summary. We report the first-ever case in the state of New Jersey of a 29-year-old male presented after a visit to a recreational water park in Texas five days before his presentation with altered mental status. In ICU, his ICP remained refractory to multiple therapies, including antibiotics and antivirals, external ventriculostomy drain, hypertonic saline, pentobarbital-induced coma, and bilateral hemicraniectomies. The CSF analysis revealed trophozoites indicating a protozoan infection, which we diagnosed in the neurocritical unit, and the patient was then immediately started with treatment that included amphotericin B, rifampin, azithromycin, and fluconazole. This suspicion was promptly confirmed by the Center for Disease Control (CDC). Unfortunately, despite all the aggressive intervention by the multidisciplinary team, the patient did not survive. Conclusion. As per the CDC, only four people out of 143 known infected individuals in the United States from 1962 to 2017 have survived. Symptoms start with a median of 5 days after exposure to contaminated water. Given the rarity of this case and its very high mortality rate, it is crucial to diagnose primary amoebic meningoencephalitis accurately as its presentation can mimic bacterial meningitis. It is vital to obtain a careful and thorough history, as it can aid in prompt diagnosis and treatment.

Nanopore sequencing improves the draft genome of the human pathogenic amoeba Naegleria fowleri

Naegleria fowleri is an environmental protist found in soil and warm freshwater sources worldwide and is known for its ability to infect humans and causing a rapid and mostly fatal primary amoebic meningoencephalitis. When contaminated water enters the nose, the facultative parasite follows the olfactory nerve and enters the brain by crossing the cribriform plate where it causes tissue damage and haemorrhagic necrosis. Although N. fowleri has been studied for several years, the mechanisms of pathogenicity are still poorly understood. Furthermore, there is a lack of knowledge on the genomic level and the current reference assembly is limited in contiguity. To improve the draft genome and to investigate pathogenicity factors, we sequenced the genome of N. fowleri using Oxford Nanopore Technology (ONT). Assembly and polishing of the long reads resulted in a high-quality draft genome whose N50 is 18 times higher than the previously published genome. The prediction of potentially secreted proteins revealed a large proportion of enzymes with a hydrolysing function, which could play an important role during the pathogenesis and account for the destructive nature of primary amoebic meningoencephalitis. The improved genome provides the basis for further investigation unravelling the biology and the pathogenic potential of N. fowleri.