Fatal subacute necrotising brainstem encephalitis in a young man due to a rare parasitic (Balamuthia) infection

Prasad, Kameshwar; Bhatia, Rupinder Singh; Srivastava, M V Padma; Pardasani, V; Garg, Avneet; Rishi, Arvind

doi:10.1136/jnnp.2007.142547

Cited by 10 publications

(8 citation statements)

References 3 publications

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“…In fact, B. mandril- (508). The clinical course of Balamuthia infection is generally subacute, often extending over a matter of weeks to months and usually concluding with the death of the patient (28,310,452,469,544). The disease spectrum of B. mandrillaris infection can include skin lesions, rhinitis (588), and disseminated disease (523).…”

Section: Balamuthia Mandrillarismentioning

confidence: 99%

“…Diagnosis by staining and microscopy of fixed tissue sections is also employed but usually after the patient's death (144). For staining of fixed tissue sections, a hematoxylin-and-eosin stain is often used (144,380,452). Other alternative stains such as a Gomori's methenamine silver stain or a periodic acid-Schiff stain are also useful (380).…”

Section: Balamuthia Mandrillarismentioning

confidence: 99%

“…As such, Balamuthia infection should not be excluded solely on the basis of a negative microscopy result. If IFAT is not available, PCR or electron microscopy may be employed to confirm the presence of a Balamuthia infection (380,452,544). DNA extracted from deparaffinized brain tissue biopsy specimens can be tested with PCR using Balamuthia-specific primers (544).…”

Section: Balamuthia Mandrillarismentioning

confidence: 99%

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Importance of Nonenteric Protozoan Infections in Immunocompromised People

et al. 2010

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SUMMARY There are many neglected nonenteric protozoa able to cause serious morbidity and mortality in humans, particularly in the developing world. Diseases caused by certain protozoa are often more severe in the presence of HIV. While information regarding neglected tropical diseases caused by trypanosomatids and Plasmodium is abundant, these protozoa are often not a first consideration in Western countries where they are not endemic. As such, diagnostics may not be available in these regions. Due to global travel and immigration, this has become an increasing problem. Inversely, in certain parts of the world (particularly sub-Saharan Africa), the HIV problem is so severe that diseases like microsporidiosis and toxoplasmosis are common. In Western countries, due to the availability of highly active antiretroviral therapy (HAART), these diseases are infrequently encountered. While free-living amoebae are rarely encountered in a clinical setting, when infections do occur, they are often fatal. Rapid diagnosis and treatment are essential to the survival of patients infected with these organisms. This paper reviews information on the diagnosis and treatment of nonenteric protozoal diseases in immunocompromised people, with a focus on patients infected with HIV. The nonenteric microsporidia, some trypanosomatids, Toxoplasma spp., Neospora spp., some free-living amoebae, Plasmodium spp., and Babesia spp. are discussed.

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Section: Balamuthia Mandrillarismentioning

confidence: 99%

Section: Balamuthia Mandrillarismentioning

confidence: 99%

Section: Balamuthia Mandrillarismentioning

confidence: 99%

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Importance of Nonenteric Protozoan Infections in Immunocompromised People

et al. 2010

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“…There is only one report from India prior to our report [9] though approximately 200 cases are reported worldwide. [1,[6][7][8] Diagnosis and treatment of GAE due to B. mandrillaris is particularly challenging because of the rarity of the disease, lack of awareness among both the clinicians and laboratory physicians and an inability to distinguish it clinically from neurotuberculosis, tuberculoma neurocysticercosis, other non-infectious aetiologies and from Acanthamoeba spp.…”

Section: Discussionmentioning

confidence: 63%

Emergence of Balamuthia mandrillaris meningoencephalitis in India

Khurana

Hallur

Goyal

et al. 2015

Indian Journal of Medical Microbiology

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“…Laurie and White et al, Inhibition of Balamuthia mandrillaris by nitroxoline 6 sulfadiazine and flucytosine while azithromycin, pentamidine isethionate, miltefosine, and voriconazole (fluconazole derivative) exhibit amoebicidal or amoebistatic activity (11,41,50). Current treatments for B. mandrillaris CNS infections employing experimental combinations of these drugs have produced inconsistent outcomes including survival in some cases and fatality in others (7,19,23,27,29,30,34,(53)(54)(55)(56)(57)(58)(59)(60)(61). As the efficacy and specificity of current treatments remains uncertain, there is a clear need to identify additional drugs that can improve patient outcomes.…”

mentioning

confidence: 99%

Repurposing the quinoline antibiotic nitroxoline to treat infections caused by the brain-eating amoebaBalamuthia mandrillaris

Retallack

et al. 2018

Preprint

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Balamuthia mandrillaris is a pathogenic free-living amoeba that causes a rare but almost always fatal infection of the central nervous system called granulomatous amoebic encephalitis (GAE). Two distinct forms of B. mandrillaris -a proliferative trophozoite form and a non-proliferative cyst form, which is highly resistant to harsh physical and chemical conditions -have been isolated from environmental samples worldwide and are both observed in infected tissue. Patients suffering from GAE are typically treated with aggressive and prolonged multi-drug regimens often including the antimicrobial agents miltefosine and pentamidine isethionate. However, survival rates remain low and studies evaluating the susceptibility of B. mandrillaris to these compounds and other potential therapeutics are limited. To address the need for more effective treatments, we screened 2,177 clinically-approved compounds for in vitro activity against B. mandrillaris. The quinoline antibiotic nitroxoline, which has safely been used in humans to treat urinary tract infections, was identified as a lead compound. We show that nitroxoline inhibits both trophozoites and cysts at low micromolar concentrations, which are within a physiologically relevant range. We compare the in vitro efficacy of nitroxoline to drugs currently used in the standard of care for GAE and find that nitroxoline is the most potent and selective inhibitor of B. mandrillaris tested. Furthermore, we demonstrate that nitroxoline prevents B. mandrillaris-mediated destruction of host cells in cultured fibroblast and primary brain explant models also at physiologically relevant concentrations. Together, our findings indicate that nitroxoline is a promising candidate for repurposing as a novel treatment of B. mandrillaris infections. Laurie and White et al., Inhibition of Balamuthia mandrillaris by nitroxoline 3 Importance Balamuthia mandrillaris is responsible for hundreds of reported cases of amoebic encephalitis, the majority of which have been fatal. Despite being an exceptionally deadly pathogen, B. mandrillaris is understudied, leaving many open questions regarding epidemiology, diagnosis, and treatment. Due to the lack of effective drugs to fight B. mandrillaris infections, mortality rates remain high even for patients receiving intensive care. This study addresses the need for new anti-amoebic drugs using a high-throughput screening approach to identify novel B. mandrillaris inhibitors. The most promising candidate identified was the quinoline antibiotic nitroxoline, which has a long history of safe use in humans.We show that nitroxoline kills B. mandrillaris at physiologically relevant concentrations and exhibits greater potency and selectivity than drugs commonly used in the current standard of care. The findings we present demonstrate the potential of nitroxoline to be an important new tool in the treatment of life threatening B. mandrillaris infections.

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Fatal subacute necrotising brainstem encephalitis in a young man due to a rare parasitic (Balamuthia) infection

Cited by 10 publications

References 3 publications

Importance of Nonenteric Protozoan Infections in Immunocompromised People

Importance of Nonenteric Protozoan Infections in Immunocompromised People

Emergence of Balamuthia mandrillaris meningoencephalitis in India

Repurposing the quinoline antibiotic nitroxoline to treat infections caused by the brain-eating amoebaBalamuthia mandrillaris

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