Chronic Meningitis in Thailand

Helbok, Raimund; Pongpakdee, Sunsanee; Yenjun, S.; Dent, Wolfgang; Beer, Ronny; Lackner, Peter; Bunyaratvej, P.; Prasert, B.; Vejjajiva, Athasit; Schmutzhard, Erich

doi:10.1159/000089236

Cited by 43 publications

(14 citation statements)

References 27 publications

(23 reference statements)

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“…In the absence of CT or MRI of the brain, common findings like headache, fever, hemiparesis and decreased level of consciousness [10] may mimic those of meningitis [4], [15]–[17]. In previous series of cerebral toxoplasmosis [18], [19], meningeal signs have been reported in 3 to 16% of the patients, although in many reports neck stiffness is not mentioned [14].…”

Section: Discussionmentioning

confidence: 99%

Cerebral Toxoplasmosis Mimicking Subacute Meningitis in HIV-Infected Patients; a Cohort Study from Indonesia

et al. 2013

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BackgroundHIV-associated subacute meningitis is mostly caused by tuberculosis or cryptococcosis, but often no etiology can be established. In the absence of CT or MRI of the brain, toxoplasmosis is generally not considered as part of the differential diagnosis.Methodology/Principal FindingsWe performed cerebrospinal fluid real time PCR and serological testing for Toxoplasma gondii in archived samples from a well-characterized cohort of 64 HIV-infected patients presenting with subacute meningitis in a referral hospital in Indonesia. Neuroradiology was only available for 6 patients.At time of presentation, patients mostly had newly diagnosed and advanced HIV infection (median CD4 count 22 cells/mL), with only 17.2% taking ART, and 9.4% PJP-prophylaxis. CSF PCR for T. Gondii was positive in 21 patients (32.8%). Circulating toxoplasma IgG was present in 77.2% of patients tested, including all in whom the PCR of CSF was positive for T. Gondii. Clinically, in the absence of neuroradiology, toxoplasmosis was difficult to distinguish from tuberculosis or cryptococcal meningitis, although CSF abnormalities were less pronounced. Mortality among patients with a positive CSF T. Gondii PCR was 81%, 2.16-fold higher (95% CI 1.04–4.47) compared to those with a negative PCR.Conclusions/SignificanceToxoplasmosis should be considered in HIV-infected patients with clinically suspected subacute meningitis in settings where neuroradiology is not available.

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Section: Discussionmentioning

confidence: 99%

Cerebral Toxoplasmosis Mimicking Subacute Meningitis in HIV-Infected Patients; a Cohort Study from Indonesia

et al. 2013

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“…It is particularly prevalent and devastating in southeast Asia and Africa, where it can cause up to 44% mortality in AIDS patients due to its nearly uniform lethality without timely and proper treatment [15]–[18]. The causative fungus Cryptococcus neoformans is ubiquitous in the environment and infects humans and other animals through inhalation.…”

Section: Introductionmentioning

confidence: 99%

Diploids in the Cryptococcus neoformans Serotype A Population Homozygous for the α Mating Type Originate via Unisexual Mating

et al. 2009

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The ubiquitous environmental human pathogen Cryptococcus neoformans is traditionally considered a haploid fungus with a bipolar mating system. In nature, the α mating type is overwhelmingly predominant over a. How genetic diversity is generated and maintained by this heterothallic fungus in a largely unisexual α population is unclear. Recently it was discovered that C. neoformans can undergo same-sex mating under laboratory conditions generating both diploid intermediates and haploid recombinant progeny. Same-sex mating (α-α) also occurs in nature as evidenced by the existence of natural diploid αADα hybrids that arose by fusion between two α cells of different serotypes (A and D). How significantly this novel sexual style contributes to genetic diversity of the Cryptococcus population was unknown. In this study, ∼500 natural C. neoformans isolates were tested for ploidy and close to 8% were found to be diploid by fluorescence flow cytometry analysis. The majority of these diploids were serotype A isolates with two copies of the α MAT locus allele. Among those, several are intra-varietal allodiploid hybrids produced by fusion of two genetically distinct α cells through same-sex mating. The majority, however, are autodiploids that harbor two seemingly identical copies of the genome and arose via either endoreplication or clonal mating. The diploids identified were isolated from different geographic locations and varied genotypically and phenotypically, indicating independent non-clonal origins. The present study demonstrates that unisexual mating produces diploid isolates of C. neoformans in nature, giving rise to populations of hybrids and mixed ploidy. Our findings underscore the importance of same-sex mating in shaping the current population structure of this important human pathogenic fungus, with implications for mechanisms of selfing and inbreeding in other microbial pathogens.

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“…Although cases of cryptococcosis in AIDS patients have decreased in developed countries due to the introduction of highly active antiretroviral therapy in the mid1990s, this disease remains responsible for up to 30% of the attributable mortality in AIDS patients in regions where highly active antiretroviral therapy is not readily available, such as Southeast Asia and Africa (7,9,12,24,25,27,28,37).…”

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confidence: 99%

Impact of Mating Type, Serotype, and Ploidy on the Virulence of Cryptococcus neoformans

et al. 2008

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Hybridization with polyploidization is a significant biological force driving evolution. The effect of combining two distinct genomes in one organism on the virulence potential of pathogenic fungi is not clear. Cryptococcus neoformans, the most common cause of fungal infection of the central nervous system, has a bipolar mating system with a and ␣ mating types and occurs as A (haploid), D (haploid), and AD hybrid (mostly diploid) serotypes. Diploid AD hybrids are derived either from a-␣ mating or from unisexual mating between haploid cells. The precise contributions of increased ploidy, the effect of hybridization between serotypes A and D, and the combination of mating types to the virulence potential of AD hybrids have remained elusive. By using in vitro and in vivo characterization of laboratory-constructed isogenic diploids and AD hybrids with all possible mating type combinations in defined genetic backgrounds, we found that higher ploidy has a minor negative effect on virulence in a murine inhalation model of cryptococcosis. The presence of both mating types a and ␣ in AD hybrids did not affect the virulence potential, irrespective of the serotype origin. Interestingly, AD hybrids with only one mating type behaved differently, with the virulence of ␣AD␣ strains similar to that of other hybrids, while aADa hybrids displayed significantly lower virulence due to negative epistatic interactions between the Aa and Da alleles of the mating type locus. This study provides insights into the impact of ploidy, mating type, and serotype on virulence and the impact of hybridization on the fitness and virulence of a eukaryotic microbial pathogen.

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Chronic Meningitis in Thailand

Cited by 43 publications

References 27 publications

Cerebral Toxoplasmosis Mimicking Subacute Meningitis in HIV-Infected Patients; a Cohort Study from Indonesia

Cerebral Toxoplasmosis Mimicking Subacute Meningitis in HIV-Infected Patients; a Cohort Study from Indonesia

Diploids in the Cryptococcus neoformans Serotype A Population Homozygous for the α Mating Type Originate via Unisexual Mating

Impact of Mating Type, Serotype, and Ploidy on the Virulence of Cryptococcus neoformans

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