[Food-borne botulism with fatal outcome in a 59-year-old woman].

Botulism is a rare and potentially fatal disease caused by toxins produced by Clostridum botulinum. This is a case report of severe and fatal food-borne botulism in a 59-year-old woman. She developed cardiac arrest shortly after admission, most likely due to paralysis of the respiratory muscles. Food botulism was suggested, and she was treated with antiserum pending confirmation of the diagnosis by detection of botulinum toxin in a serum sample. The source of botulism was never confirmed, but was likely to be home-canned fish.

Prognostic factors of 90-day mortality in patients hospitalised with COVID-19.

INTRODUCTION: Mortality due to COVID-19 is higher among elderly patients with comorbidities. Even so, prognostication in COVID-19 remains limited. METHODS: We assessed 90-day mortality stratified by comorbidities, routine biochemical markers and oxygen need in a consecutive single-centre cohort from 2 March to 2 June 2020. RESULTS: We included 263 hospitalised patients with laboratory-confirmed COVID-19. On admission, fitness for intensive care was determined in 254 patients including 98 (39%) with a do-not-resuscitate order. Ninety-day overall mortality was 29%, whereas intensive care unit (ICU) mortality was 35% (14/40). Alcohol abuse, liver disease and elevated urea were strongly associated with mortality in univariable analyses. In a mutually adjusted multivariable analysis, we found an independent incremental increase in 90-day mortality with each increasing age by decade (hazard ratio (HR) = 1.5; 95% confidence interval (CI): 1.2-1.9), Charlson Comorbidity Index (CCI) score (HR = 1.2; 95% CI: 1.0-1.4), number of abnormal blood tests (HR = 1.2; 95% CI: 1.1-1.3) and l/min. of supplemental oxygen (HR = 1.1; 95% CI: 1.1-1.2). CONCLUSIONS: The overall mortality was similar to that of other hospitalised patients, whereas the ICU mortality was lower than expected. On admission, each additional age by decade, CCI score, number of abnormal blood tests and magnitude of supplemental oxygen were independently associated with increased mortality. FUNDING: none. TRIAL REGISTRATION: not relevant.

Purification and initial characterization of Plasmodium falciparum K+ channels, PfKch1 and PfKch2 produced in Saccharomyces cerevisiae.

Resistance towards known antimalarial drugs poses a significant problem, urging for novel drugs that target vital proteins in the malaria parasite Plasmodium falciparum. However, recombinant production of malaria proteins is notoriously difficult. To address this, we have investigated two putative K+ channels, PfKch1 and PfKch2, identified in the P. falciparum genome. We show that PfKch1 and PfKch2 and a C-terminally truncated version of PfKch1 (PfKch11-1094) could indeed be functionally expressed in vivo, since a K+-uptake deficient Saccharomyces cerevisiae strain was complemented by the P. falciparum cDNAs. PfKch11-1094-GFP and GFP-PfKch2 fusion proteins were overexpressed in yeast, purified and reconstituted in lipid bilayers to determine their electrophysiological activity. Single channel conductance amounted to 16 ± 1 pS for PfKch11-1094-GFP and 28 ± 2 pS for GFP-PfKch2. We predicted regulator of K+-conductance (RCK) domains in the C-terminals of both channels, and we accordingly measured channel activity in the presence of Ca2+.

[Melioidosis is a rare diagnosis among returning travellers with fever].

The causative organism of melioidosis is Burkholderia pseudomallei, a Gram-negative bacterium endemic to Southeast Asia and Northern Australia. The clinical presentation varies, ranging from asymptomatic cases to rapidly progressive septicaemia and shock. Abscesses may be found in any internal organ. We describe an infrequent presentation of melioidosis with various symptoms, including haematuria and rectal pain. Perirectal and prostatic abscesses were found, the causative organism was identified and relevant treatment administered, resulting in a full recovery.

Functional characterization of malaria parasites deficient in the K+ channel Kch2.

K+ channels are integral membrane proteins, which contribute to maintain vital parameters such as the cellular membrane potential and cell volume. Malaria parasites encode two K+ channel homologues, Kch1 and Kch2, which are well-conserved among members of the Plasmodium genus. In the rodent malaria parasite P. berghei, the functional significance of K+ channel homologue PbKch2 was studied using targeted gene knock-out. The knockout parasites were characterized in a mouse model in terms of growth-kinetics and infectivity in the mosquito vector. Furthermore, using a tracer-uptake technique with 86Rb+ as a K+ congener, the K+ transporting properties of the knockout parasites were assessed. RESULTS: Genetic disruption of Kch2 did not grossly affect the phenotype in terms of asexual replication and pathogenicity in a mouse model. In contrast to Kch1-null parasites, Kch2-null parasites were fully capable of forming oocysts in female Anopheles stephensi mosquitoes. 86Rb+ uptake in Kch2-deficient blood-stage P. berghei parasites (Kch2-null) did not differ from that of wild-type (WT) parasites. About two-thirds of the 86Rb+ uptake in WT and in Kch2-null parasites could be inhibited by K+ channel blockers and could be inferred to the presence of functional Kch1 in Kch2 knockout parasites. Kch2 is therefore not required for transport of K+ in P. berghei and is not essential to mosquito-stage sporogonic development of the parasite.

[Miliary tuberculosis is difficult to diagnose].

An 82-year-old male was admitted for treatment for pneumonia after a few weeks of fever, cough and dyspnoea. Alternating treatment with different antibiotics had no effect on the condition and all common tests for tuberculosis were negative. An autopsy later revealed disseminated tuberculosis to lungs, retroperitoneal glands and liver. Miliary tuberculosis can in principle affect all organ systems and a wide variety of unspecific symptoms are seen. The differential diagnosis should be brought to the awareness of clinicians when complex symptomatology remains unaccounted for.

[Capnocytophaga canimorsus meningitis diagnosed by means of a 16S rRNA analysis]. / Capnocytophaga canimorsus-meningitis diagnosticeret ved hjælp af 16S rRNA-analyse.

Capnocytophaga canimorsus is a gram-negative bacterial species hosted in the oral cavity of dogs. C. canimorsus can cause sepsis, meningitis and endocarditis. Penicillin is the drug of choice. However, the species is a slow-grower and sometimes missed in blood cultures. Patients with a history of alcoholism, splenectomy or immunodeficiency are at an increased risk of contracting serious infections with C. canimorsus following dog bites. We report a case story of C. canimorsus meningitis contracted after a dog bite.

Critical role of a K+ channel in Plasmodium berghei transmission revealed by targeted gene disruption.

Regulated K(+) transport across the plasma membrane is of vital importance for the survival of most cells. Two K(+) channels have been identified in the Plasmodium falciparum genome; however, their functional significance during parasite life cycle in the vertebrate host and during transmission through the mosquito vector remains unknown. We hypothesize that these two K(+) channels mediate the transport of K(+) in the parasites, and thus are important for parasite survival. To test this hypothesis, we identified the orthologue of one of the P. falciparum K(+) channels, PfKch1, in the rodent malaria parasite P. berghei (PbKch1) and examined the biological role by performing a targeted disruption of the gene encoding PbKch1. The deduced amino acid sequence of the six transmembrane domains of PfKch1 and PbKch1 share 82% identity, and in particular the pore regions are completely identical. The PbKch1-null parasites were viable despite a marked reduction in the uptake of the K(+) congener (86)Rb(+), and mice infected with PbKch1-null parasites survived slightly longer than mice infected with WT parasites. However, the most striking feature of the phenotype was the virtually complete inhibition of the development of PbKch1-null parasites in Anopheles stephensi mosquitoes. In conclusion, these studies demonstrate that PbKch1 contributes to the transport of K(+) in P. berghei parasites and supports the growth of the parasites, in particular the development of oocysts in the mosquito midgut. K(+) channels therefore may constitute a potential antimalarial drug target.

[Transport proteins as drug targets in Plasmodium falciparum. New perspectives in the treatment of malaria]. / Transportproteiner som drug-targets hos Plasmodium falciparum. Nye perspektiver i behandlingen af malaria.

The malaria parasite, Plasmodium falciparum, infects and replicates in human erythrocytes. Through the use of substrate-specific transport proteins, P. falciparum takes up nutrients from the erythrocyte's cytoplasm. The sequencing and publishing of the P. falciparum genome have made it possible to identify, clone and characterise a number of these transport proteins from the parasite. Since the P. falciparum transport proteins differ from their human homologues, they may provide potential drug targets in the treatment of malaria. An example of a P. falciparum transport protein which seems promising as a drug target is the parasite's hexose transporter. Furthermore, the antimalarial drug artemisinin has been shown to interact specifically with the parasite's Ca2+ pump. A number of other transport proteins are also discussed as possible drug targets.

Molecular cloning of a K(+) channel from the malaria parasite Plasmodium falciparum.

In most living cells, K(+) channels are important for the generation of the membrane potential and for volume regulation. The parasite Plasmodium falciparum, which causes malignant malaria, must be able to deal with large variations in the ambient K(+) concentration: it is exposed to high concentrations of K(+) when inside the erythrocyte and low concentrations when in plasma. In the recently published genome of P. falciparum, we have identified a gene, pfkch1, encoding a potential K(+) channel, which to some extent resembles the big-conductance (BK) K(+) channel. We have cloned the approximately 6000 nucleotide (nt) fragment from cDNA, studied the pattern of expression of pfkch1 throughout the intraerythrocytic part of the parasite's life-cyclus, and characterized the channel on the basis of similarity to other K(+) channels from pro- and eukaryotic organisms. This P. falciparum K(+) channel could be a potential drug target.