In the Literature

Candida Krusei/Pichia Kudriavzevii: A Rose by any other Name …

Douglass AP, Offei B, Braun-Galleani S, et al. Population genomics shows no distinction between pathogenic Candida krusei and environmental Pichia kudriavzevii: one species, four names. PLoS Pathog 2018; 14:e1007138. doi:10.1371/journal.ppat.1007138.

Candida krusei is a human pathogen that, while accounting for only approximately 2% of invasive Candida infections, is of note because of its intrinsic resistance to fluconazole and several other azole antifungals as a result of poor affinity for Erg11 together with constitutive expression of Abc1 and Abc11 efflux pumps. While generally considered to be susceptible to echinocandins, recent reports indicate a poor correlation of in vitro susceptibility results with caspofungin (and amphotericin B) with efficacy in a neutropenic mouse model [1]. Furthermore, failure of caspofungin therapy with rapid emergence of resistance associated with FKS1 hot spot mutations has been reported in a patient with acute lymphocytic leukemia [2].

Pichia kudriavzevii is a yeast widely distributed in the environment that is used in traditional fermentations such as of cassava and milk and also, for example, in starter cultures for sourdough bread. It is categorized as generally safe by the US Food and Drug Administration and has been considered as a candidate probiotic. Despite this sanguine assessment, P. kudriavzevii has been suggested to actually be the teleomorph (sexual form) of the known pathogen, C. krusei. To evaluate whether these 2 yeasts are basically the same organism, Douglass and colleagues set out to determine the genetic relatedness of P. kudriavzevii and C. krusei by sequencing the type strains as well as environmental and clinical isolates. The investigators, by demonstration of 99.6% DNA identity, confirmed that they did represent the same species. Furthermore, clinical and environmental isolates were not distinct and the latter, like clinical isolates, were also resistant to fluconazole.

The investigators indicate that the organism has additional aliases. One, Issatchenkia orientalis, has been obsolete since its replacement by P. kudriavzevii, while another is Candida glycerinogenes. Under the now-obsolete name, the organism has been used in viniculture and oenology, whereas under the latter designation it is used for industrial production of glycerol.

As the authors point out, calling an organism “Candida” often has limited phylogenetic relevance. C. krusei/P. kudriavzevii, assigned to the genus Pichia in the family Pichiaceae, Candida albicans (family Debaryomycetaceae), and Candida glabrata (family Saccharomycetaceae) “are as distantly related to each other as humans are to sea squirts.” The resolution of phylogenetic and nomenclature issues is important in our understanding of issues, for example, that the widespread use in industry and possibly as a probiotic of a yeast under the name P. kudriavzevii may involve widespread exposure to an antifungal-resistant human pathogen with the name C. krusei. Fortunately, as pointed out to me by Ferric Fang, there is hope that the confusion will be mitigated as the result of a decision made at the International Botanical Congress (yes – Botanical!) in 2011 to discontinue dual nomenclature of pleomorphic fungi—that is, “one fungus, one name” [3, 4].

References

An Examination of Persisting Health Effects of Neuroborreliosis

Obel N, Dessau RB, Krogfelt KA, et al. Long term survival, health, social functioning, and education in patients with European Lyme neuroborreliosis: nationwide population based cohort study. BMJ 2018; 361:k1998.

Neuroborreliosis is caused by infection with Borrelia burgdorferi sensu lato complex organisms, with most cases in the United States due to infection with B. burgdorferi sensu stricto, whereas Borrelia afzelii and Borrelia garinii are more frequent in Europe and Asia. While it appears that individual subspecies may lead to differing proportions of clinical syndromes, such as the apparently greater frequency of occurrence of Bannwarth syndrome (subacute painful meningoradiculitis) in Europe where it is often associated with B. garinii infection, the outcomes of each syndrome appear similar.

In both the United States and Europe, some patients report prolonged symptoms for months to years after resolution of the acute infection, and a recent systematic review found a 28% prevalence of such residual symptoms [1]. Few of the reviewed studies, however, included controls and some did not even indicate whether laboratory confirmation was required for inclusion, which, together with the subjectivity of reported symptoms, makes it difficult to assign an etiological relationship.

Obel and colleagues evaluated the long-term effects of neuroborreliosis using a population-based nationwide cohort study. All 2067 Danish residents with laboratory-proven B. burgdorferi sensu stricto infection during 1998–2016 were included, as were 20670 population controls matched by sex and date of birth. The investigators found no evidence of increased mortality or of differences in educational and social outcomes. There was no increased risk of multiple sclerosis, as has been previously asserted. There was, however, a significant but unexplained increased risk of hematological malignancies and of nonmelanoma skin cancers in the study group. A number of other findings were difficult to explain, such as a greater marriage rate and lesser divorce rate in the neuroborreliosis cohort, as well as, in those who had their infection as children, higher elementary school mathematics marks and a higher rate of completion of high school studies. While these unexpected findings, especially those related to malignancy risk, may deserve further examination, it can be concluded that, overall, neuroborreliosis is not associated with an increased risk of symptoms interfering with having a healthy and productive life. It is likely that this conclusion applies to neuroborreliosis acquired in the United States as well, but since the etiologic genotypes there often differ from those in Europe, this requires confirmation.

Reference

Case Vignette: Uncooked Centipedes and Angiostrongyliasis

Wang H, Lu L, She D, et al. Eating centipedes can result in Angiostrongylus cantonensis infection: two case reports and pathogen investigation. Am J Trop Med Hyg 2018; 99:743–8.

A 78-year-old woman was admitted to a hospital in Guangzhou, China, because of headache, somnolence, and cognitive impairment that had been present for several weeks. A lumbar puncture was performed and detected an opening pressure of 26 cm H₂O; cerebrospinal fluid (CSF) protein was 137 mg/dL and glucose was 53 mg/dL, while the white blood cell count was 600 cells/µL with 40 eosinophils/µL. Peripheral eosinophilia (30%) was also present. Magnetic resonance imaging with fluid attenuation inversion recovery sequence demonstrated increased signal in the left midbrain and right frontal lobes. Immunoglobulin G and immunoglobulin M antibodies directed against antigens of Angiostrongylus cantonensis were detected in CSF. Her clinical status and CSF (including opening pressure) improved after receipt of albendazole and dexamethasone.

A second patient, a 46-year-old man, also presented with meningoencephalitis due to A. cantonensis with similar findings and also recovered after the same treatment. Both patients reported occasionally eating raw centipedes.

The authors purchased 20 centipedes that had been caught in the wild in Guanxi Province at the local Quinping market. They were able to detect third-stage larvae in 7 of the 20 centipedes with a mean of 56 larvae in each.

Human infection generally occurs after the inadvertent ingestion of mature larvae in mollusks such as snails and slugs, as well as of monitor lizards, frogs, and fish. Thailand, China, and Taiwan have the highest prevalences of A. cantonensis (rat lungworm) infection. In China, the main sources are the African giant land snail and the apple snail. Centipedes have not previously been reported to be a source of infection.

While most cases of angiostrongyliasis occur in Asia and the Pacific Islands (including Hawaii), occasional autochthonous infections occur in the continental United States. The Centers for Disease Control and Prevention recently indicated that 12 cases of eosinophilic meningitis due to A. cantonensis had been reported to them from January 2011 through January 2017, and 6 of these were likely to have been autochthonous with acquisition in the southern United States [1]. None of the 12 patients reported eating raw centipedes.

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