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The First Molecular Genotyping of Naegleria fowleri Causing Primary Amebic Meningoencephalitis in Thailand With Epidemiology and Clinical Case Reviews

ABSTRACT: Primary amebic meningoencephalitis (PAM) is a rare and fatal central nervous system infection caused by Naegleria fowleri, a free-living amoeba found in the environment. To date, eight pathogenic N. fowleri genotypes have been reported worldwide. We aimed to explore the genotypes of N. fowleri that cause primary amebic meningoencephalitis in Thailand. In 2021, the 17th PAM case was reported, and a retrospective literature search of PAM cases in Thailand from 1982 through April 2021 was performed. Phylogenetic and genotyping analyses of the two mitochondrial (12S rRNA and 16S rRNA) and nuclear (ITS1 and 5.8s rRNA) genes of N. fowleri were performed on four available clinical isolates. Based on the mitochondrial and nuclear genes, N. fowleri genotype T3 was found to cause PAM in three out of four cases. However, disagreement between the genotype based on the mitochondrial and nuclear genes was found in one of the PAM cases, in which the 12S rRNA locus suggested the causative genotype as T1, while the ITS1 implied genotype T4. The discrepancy between the mitochondrial and nuclear genome was previously observed, which suggests the possible horizontal gene transfer among N. fowleri species. Based on the ITS1 gene, two N. fowleri genotypes, T3 and T4, were found to be the genotypes causing PAM in this study. In addition, N. fowleri genotype T2 was previously reported in a traveler who was infected in Thailand. Thus, at least three genotypes (T2, T3, and T4) of N. fowleri are found to be associated with PAM in Thailand.

SUBMITTER: Soontrapa P

PROVIDER: S-EPMC9326084 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Corrigendum: The first molecular genotyping of Naegleria fowleri causing primary amebic meningoencephalitis in Thailand with epidemiology and clinical case reviews.

Project description:[This corrects the article DOI: 10.3389/fcimb.2022.931546.].

| S-EPMC9559716 | biostudies-literature

Epidemiology and Clinical Characteristics of Primary Amebic Meningoencephalitis Caused by Naegleria fowleri: A Global Review.

Project description:BackgroundPrimary amebic meningoencephalitis (PAM) is a rapidly progressive and often fatal condition caused by the free-living ameba Naegleria fowleri. To estimate the global occurrence, characterize the epidemiology, and describe the clinical features of PAM, we report a series of PAM cases published in the international literature and reported to the Centers for Disease Control and Prevention (CDC).MethodsWe performed a literature search of PAM case reports published through 2018. Additionally, we included cases reported through the CDC's Free-Living Ameba surveillance or diagnosed via CDC's Free-Living and Intestinal Amebas Laboratory. Cases were classified as confirmed, probable, or suspect on the basis of confirmatory testing, presentation, exposure, and disease course.ResultsA total of 381 PAM cases were identified. Seven reported survivors were classified as confirmed. The most commonly reported exposure associated with PAM was swimming/diving, and the most common class of water source was lakes/ponds/reservoirs. Patients were predominantly male (75%), with a median age of 14 years. Confirmed and probable cases were similar in their survival, course of illness, and cerebrospinal fluid (CSF) findings.ConclusionsPAM is a rare but deadly disease with worldwide occurrence. Improved clinician awareness, resulting in earlier diagnosis and treatment, may contribute to increased survival among PAM patients. The case definition of probable used in this study appears to capture cases of PAM, as evidenced by similarities in outcomes, clinical course, and CSF profile to confirmed cases. In the absence of confirmatory testing, clinicians could use this case definition to identify cases of PAM.

| S-EPMC8739754 | biostudies-literature

Role of cathepsin B of Naegleria fowleri during primary amebic meningoencephalitis.

Project description:Naegleria fowleri causes primary amoebic meningoencephalitis in humans and experimental animals. It has been suggested that cysteine proteases of parasites play key roles in metabolism, nutrient uptake, host tissue invasion, and immune evasion. The aim of this work was to evaluate the presence, expression, and role of cathepsin B from N. fowleri in vitro and during PAM. Rabbit-specific polyclonal antibodies against cathepsin B were obtained from rabbit immunization with a synthetic peptide obtained by bioinformatic design. In addition, a probe was designed from mRNA for N. fowleri cathepsin B. Both protein and messenger were detected in fixed trophozoites, trophozoites interacted with polymorphonuclear and histological sections of infected mice. The main cathepsin B distribution was observed in cytoplasm or membrane mainly pseudopods and food-cups while messenger was in nucleus and cytoplasm. Surprisingly, both the messenger and enzyme were observed in extracellular medium. To determine cathepsin B release, we used trophozoites supernatant recovered from nasal passages or brain of infected mice. We observed the highest release in supernatant from recovered brain amoebae, and when we analyzed molecular weight of secreted proteins by immunoblot, we found 30 and 37 kDa bands which were highly immunogenic. Finally, role of cathepsin B during N. fowleri infection was determined; we preincubated trophozoites with E-64, pHMB or antibodies with which we obtained 60%, 100%, and 60% of survival, respectively, in infected mice. These results suggest that cathepsin B plays a role during pathogenesis caused by N. fowleri mainly in adhesion and contributes to nervous tissue damage.

| S-EPMC9485797 | biostudies-literature

Fatal Primary Amebic Meningoencephalitis due to Naegleria fowleri: The First Imported Case in Korea.

Project description:Primary amebic meningoencephalitis (PAM) is a rare, but almost always fatal, central nervous system infection caused by Naegleria fowleri, which are thermophilic free-living amoeba. Here, we report the first case of PAM detected in South Korea, probably imported from Thailand. Despite antimicrobial treatment for N. fowleri infection with a combination of intravenous liposomal amphotericin B, fluconazole, azithromycin, and oral rifampin, the patient died 13 days after the onset of symptoms. Clinicians in South Korea treating severe meningoencephalitis, especially in individuals returning from tropical areas, are encouraged to include PAM in the differential diagnoses, given the accelerated global warming and increased overseas trips.

| S-EPMC10522881 | biostudies-literature

Fatal Case of Naegleria fowleri Primary Amebic Meningoencephalitis from Indoor Surfing Center, Taiwan, 2023.

Project description:We investigated a fatal case of primary amoebic meningoencephalitis from an indoor surfing center in Taiwan. The case was detected through encephalitis syndromic surveillance. Of 56 environmental specimens, 1 was positive for Naegleria fowleri ameba. This report emphasizes the risk for N. fowleri infection from inadequately disinfected recreational waters, even indoors.

| S-EPMC11346987 | biostudies-literature

Isolation and molecular typing of Naegleria fowleri from the brain of a cow that died of primary amebic meningoencephalitis.

Project description:Naegleria fowleri causes an acute and rapidly fatal central nervous system infection called primary amebic meningoencephalitis (PAM) in healthy children and young adults. We describe here the identification of N. fowleri isolated from the brain of one of several cows that died of PAM based on sequencing of the internal transcribed spacers, including the 5.8S rRNA genes.

| S-EPMC1233957 | biostudies-literature

Naegleria fowleri Meningoencephalitis Associated with Public Water Supply, Pakistan, 2014.

Project description: Not available

| S-EPMC5038392 | biostudies-literature

Case Report and Literature Review: Bacterial Meningoencephalitis or Not? Naegleria fowleri Related Primary Amoebic Meningoencephalitis in China.

Project description:In China, a 9-year-old boy was transferred to the hospital with fever, vomiting, and headache. The disease rapidly deteriorated into vague consciousness. Applying conventional clinical examinations such as blood and cerebrospinal fluid (CSF) tests, the diagnosis of bacterial meningoencephalitis was first drawn, and expectant treatments were adopted immediately. However, the symptoms did not alleviate, adversely, this boy died 3 days after admission. Considering the skeptical points of the duration, such as the unknown infectious bacteria and the pathogen invasion path, blood and CSF samples were then sent for metagenomic next-generation sequencing (mNGS) to ascertain the cause of death. The 42,899 and 1,337 specific sequences of N. fowleri were detected by mNGS in the CSF sample and the blood sample, respectively. PCR results and pathological smear subsequently confirmed the mNGS detection. The patient was finally diagnosed as primary amoebic meningoencephalitis. Besides, in this article, 15 similar child infection cases in the past 10 years are summarized and analyzed to promote the early diagnosis of this rare disease.

| S-EPMC9033202 | biostudies-literature

Fatal meningoencephalitis in child and isolation of Naegleria fowleri from hot springs in Costa Rica.

Project description: Not available

| S-EPMC4313663 | biostudies-literature

A case of Naegleria fowleri related primary amoebic meningoencephalitis in China diagnosed by next-generation sequencing.

Project description:BackgroundPrimary amoebic meningoencephalitis (PAM), caused by Naegleria fowleri, is a rare protozoan infectious disease in China. A fatality rate of over 95% had been reported due to extremely rapid disease progression in the USA and other countries. Rapid and precise identification of the causative agent is very important to clinicians for guiding their choices for administering countermeasures in the clinic. In this report, we applied the next-generation sequencing (NGS) method to rapidly show that N. fowleri was the causative agent of a fatal case involving a 42-year-old man with severe PAM disease, the first reported in mainland China.Case presentationA 42-year old male in a deep coma was admitted to Shenzhen Third People's Hospital, a special medical care unit with expertise in infectious diseases. Increased intracranial pressure was detected. The cerebrospinal fluid (CSF) sample was found to be red and cloudy with increased leukocyte and protein levels. While bacterial cultures with CSF were negative, N. fowleri was determined to be the causative agent with NGS. Amphotericin B (AmB), a drug with anti-amoeba activity, was used immediately, but the treatment came too late and the patient died 2 days after the NGS confirmation.ConclusionIn this paper, we reported a case of PAM disease for the first time in mainland China. NGS was used for rapid diagnosis and provided guidance for prescribing medications. However, the patient died due to a late admission amid advanced PAM disease. Early detection of N. fowleri is necessary in order to select effective drug treatments and control the disease progression. Despite the negative survival outcome, NGS was shown to be a promising method of rapid and precise identification of N. fowleri.

| S-EPMC6064090 | biostudies-literature

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