Acanthamoeba meningoencephalitis in immunocompetent: A case report and review of literature

Khanna, Vinay K.; Shastri, B Ananthakrishna; Anusha, G K; Mukhopadhayay, Chiranjay; Khanna, Ruchee

doi:10.4103/2229-5070.138540

Cited by 18 publications

(13 citation statements)

References 14 publications

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“…[ 5 ] Until recently, no more than a dozen patients out of ~350 reported PAM cases worldwide have been treated successfully with Amphotericin B (AmpB), either alone or in combination with other drugs. [ 6 – 9 ]. The investigational anti-cancer and anti-leishmaniasis agent miltefosine[ 10 ] showed promise, but not all patients who received miltefosine as part of their treatment regimens survived.…”

Section: Introductionmentioning

confidence: 99%

Enzymatic chokepoints and synergistic drug targets in the sterol biosynthesis pathway of Naegleria fowleri

et al. 2018

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Naegleria fowleri is a free-living amoeba that can also act as an opportunistic pathogen causing severe brain infection, primary amebic meningoencephalitis (PAM), in humans. The high mortality rate of PAM (exceeding 97%) is attributed to (i) delayed diagnosis, (ii) lack of safe and effective anti-N. fowleri drugs, and (iii) difficulty of delivering drugs to the brain. Our work addresses identification of new molecular targets that may link anti-Naegleria drug discovery to the existing pharmacopeia of brain-penetrant drugs. Using inhibitors with known mechanism of action as molecular probes, we mapped the sterol biosynthesis pathway of N. fowleri by GC-MS analysis of metabolites. Based on this analysis, we chemically validated two enzymes downstream to CYP51, sterol C24-methyltransferase (SMT, ERG6) and sterol Δ8−Δ7 -isomerase (ERG2), as potential therapeutic drug targets in N. fowleri. The sterol biosynthetic cascade in N. fowleri displayed a mixture of canonical features peculiar to different domains of life: lower eukaryotes, plants and vertebrates. In addition to the cycloartenol→ergosterol biosynthetic route, a route leading to de novo cholesterol biosynthesis emerged. Isotopic labeling of the de novo-synthesized sterols by feeding N. gruberi trophozoites on the U13C-glucose-containing growth medium identified an exogenous origin of cholesterol, while 7-dehydrocholesterol (7DHC) had enriched 13C-content, suggesting a dual origin of this metabolite both from de novo biosynthesis and metabolism of scavenged cholesterol. Sterol homeostasis in Naegleria may be orchestrated over the course of its life-cycle by a “switch” between ergosterol and cholesterol biosynthesis. By demonstrating the growth inhibition and synergistic effects of the sterol biosynthesis inhibitors, we validated new, potentially druggable, molecular targets in N. fowleri. The similarity of the Naegleria sterol Δ8−Δ7 -isomerase to the human non-opioid σ1 receptor, implicated in human CNS conditions such as addiction, amnesia, pain and depression, provides an incentive to assess structurally diverse small-molecule brain-penetrant drugs targeting the human receptor for anti-Naegleria activity.

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Section: Introductionmentioning

confidence: 99%

Enzymatic chokepoints and synergistic drug targets in the sterol biosynthesis pathway of Naegleria fowleri

et al. 2018

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“…Most of the time accidental detection of Acanthamoeba was reported in clinical samples [ [8] , [9] , [10] ]. Khanna et al.…”

Section: Discussionmentioning

confidence: 99%

“…Khanna et al. reported a case which was clinically suspected extrapulmonary tuberculosis, after microbiological evaluation diagnosis was changed to Acanthamoeba meningitis and treated successfully [ 9 ].Histologically few cases of Acanthamoeba had been mistakenly diagnosed as a case of inflammatory debris and histiocytes as well as Yeast in another case [ 10 , 11 ]. In present study, patient might have acquired the infection through the respiratory route and comorbidity diabetes and steroid therapy had made more prone for this infection.…”

Section: Discussionmentioning

confidence: 99%

Acanthamoeba species from a post-covid patient with CSF rhinorrhea; a next possible post covid menace? A case report

Keche¹,

Chakravarty²,

Khatoon³

et al. 2023

Indian Journal of Medical Microbiology

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“…Case reports of Acanthamoeba infecting immunocompetent patients [8][9][10][11] show different imaging findings and outcome (Table 1). Hydrocephalus was not present in any of these [11,12].…”

Section: Discussionmentioning

confidence: 99%

Acanthamoeba meningoencephalitis with hydrocephalus in an immunocompetent patient: A case report

Singh¹,

Sahu²,

Singh³

et al. 2020

IJCR

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A canthamoeba meningoencephalitis is caused by free-living ameba Acanthamoeba. These usually infect immunocompromised persons and have a high fatality. Acanthamoeba causes granulomatous encephalitis and meningoencephalitis along with keratitis, sinusitis, and cutaneous lesions [1,2]. Acanthamoeba infection of the brain has a high mortality [3]. Acanthamoeba meningoencephalitis presenting as hydrocephalus in an immunocompetent individual is a rare disorder. Ventriculoperitoneal shunting along with anti-Acanthamoeba medications is curative and leads to the resolution of symptoms in such patients. Several case reports are present in the literature regarding the infection of Acanthamoeba meningoencephalitis in immunocompetent patients, but the patients reported did not presented with hydrocephalus. We present a rare case of Acanthamoeba meningoencephalitis with hydrocephalus diagnosed at cerebrospinal fluid (CSF) examination in an immunocompetent young patient.

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Acanthamoeba meningoencephalitis in immunocompetent: A case report and review of literature

Cited by 18 publications

References 14 publications

Enzymatic chokepoints and synergistic drug targets in the sterol biosynthesis pathway of Naegleria fowleri

Enzymatic chokepoints and synergistic drug targets in the sterol biosynthesis pathway of Naegleria fowleri

Acanthamoeba species from a post-covid patient with CSF rhinorrhea; a next possible post covid menace? A case report

Acanthamoeba meningoencephalitis with hydrocephalus in an immunocompetent patient: A case report

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