Systematic Analysis of Copy Number Variations in the Pathogenic Yeast Candida parapsilosis Identifies a Gene Amplification in RTA3 That is Associated with Drug Resistance

We analyzed the genomes of 170 C. parapsilosis isolates and identified multiple copy number variations (CNVs). We identified two genes, RTA3 (CPAR2_104610) and ARR3 (CPAR2_601050), each of which was the target of multiple independent amplification events. Phylogenetic analysis shows that most of these amplifications originated only once. For ARR3, which encodes a putative arsenate transporter, 8 distinct CNVs were identified, ranging in size from 2.3 kb to 10.5 kb with 3 to 23 copies. For RTA3, 16 distinct CNVs were identified, ranging in size from 0.3 kb to 4.5 kb with 2 to ~50 copies. One unusual amplification resulted in a DUP-TRP/INV-DUP structure similar to some human CNVs. RTA3 encodes a putative phosphatidylcholine (PC) floppase which is known to regulate the inward translocation of PC in Candida albicans. We found that an increased copy number of RTA3 correlated with resistance to miltefosine, an alkylphosphocholine drug that affects PC metabolism. Additionally, we conducted an adaptive laboratory evolution experiment in which two C. parapsilosis isolates were cultured in increasing concentrations of miltefosine. Two genes, CPAR2_303950 and CPAR2_102700, coding for putative PC flippases homologous to S. cerevisiae DNF1 gained homozygous protein-disrupting mutations in the evolved strains. Overall, our results show that C. parapsilosis can gain resistance to miltefosine, a drug that has recently been granted orphan drug designation approval by the United States Food and Drug Administration for the treatment of invasive candidiasis, through both CNVs or loss-of-function alleles in one of the flippase genes

Severe malaria in Europe: an 8-year multi-centre observational study

Background: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria. Methods: The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria. Results: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate. Conclusion: The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up to detect and manage late haemolytic events

High prevalence of asymptomatic malaria infections in adults, Ashanti Region, Ghana, 2018

Background!#!Ghana is among the high-burden countries for malaria infections and recently reported a notable increase in malaria cases. While asymptomatic parasitaemia is increasingly recognized as a hurdle for malaria elimination, studies on asymptomatic malaria are scarce, and usually focus on children and on non-falciparum species. The present study aims to assess the prevalence of asymptomatic Plasmodium falciparum and non-falciparum infections in Ghanaian adults in the Ashanti region during the high transmission season.!##!Methods!#!Asymptomatic adult residents from five villages in the Ashanti Region, Ghana, were screened for Plasmodium species by rapid diagnostic test (RDT) and polymerase chain reaction (PCR) during the rainy season. Samples tested positive were subtyped using species-specific real-time PCR. For all Plasmodium ovale infections additional sub-species identification was performed.!##!Results!#!Molecular prevalence of asymptomatic Plasmodium infection was 284/391 (73%); only 126 (32%) infections were detected by RDT. While 266 (68%) participants were infected with Plasmodium falciparum, 33 (8%) were infected with Plasmodium malariae and 34 (9%) with P. ovale. The sub-species P. ovale curtisi and P. ovale wallikeri were identified to similar proportions. Non-falciparum infections usually presented as mixed infections with P. falciparum.!##!Conclusions!#!Most adult residents in the Ghanaian forest zone are asymptomatic Plasmodium carriers. The high Plasmodium prevalence not detected by RDT in adults highlights that malaria eradication efforts must target all members of the population. Beneath Plasmodium falciparum, screening and treatment must also include infections with P. malariae, P. o. curtisi and P. o. wallikeri

Career Prospects for Young Physicians in Infectious Diseases

Infectious Diseases are a cross-sectional area connected to various medical disciplines and offer interested physicians multiple working opportunities. The spectrum of infectious diseases covers both out- and inpatient care as well as basic, clinical and epidemiological research. The need for infectious diseases specialists is increasing, thus career prospects are promising. Working conditions in infectious diseases are comparatively family-friendly. With this article we intend to arouse interest for working in the fascinating fields of infectious diseases and provide information on career opportunities. Data from a recently conducted survey among members of the German Society of Infectious Diseases deliver insight, how infectious disease specialists work today

Hematogenous dissemination of Candida dubliniensis causing spondylodiscitis and spinal abscess in a HIV-1 and HCV-coinfected patient

We report a case of spondylodiscitis and spinal abscess following haematogenous dissemination of the emerging yeast Candida dubliniensis in a human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV)-coinfected patient. Although C. dubliniensis is considered less virulent compared to its closest known relative Candida albicans, reports of severe fungal infections are increasing. This case indicates that the pathogenicity of C. dubliniensis may be higher than previously believed. Therefore fungal infections caused by this dimorph fungus should be kept in mind in immunocompromised patients with spondylodiscitis and spinal abscess

Response to fever and utilization of standby emergency treatment (SBET) for malaria in travellers to Southeast Asia: a questionnaire-based cohort study

Background: Guidelines in several European countries recommend standby emergency treatment (SBET) for travellers to regions with low or medium malaria transmission instead of continuous chemoprophylaxis: travellers are advised to seek medical assistance within 24 h in case of fever and to self-administer SBET only if they are not able to consult a doctor within the time period specified. Data on healthcare-seeking behaviour of febrile travellers and utilization of SBET is however scarce as only two studies were performed in the mid-1990s. Since tourism is constantly increasing and malaria epidemiology has dramatically changed in the meantime more knowledge is urgently needed. Methods: Some 876 travellers to destinations in South and Southeast Asia with low or medium malaria transmission were recruited in the travel clinic of the University Medical Center Hamburg-Eppendorf. Demographic and travel-related data were collected by using questionnaires. Pre-travel advice was carried out and SBET was prescribed in accordance to national guidelines. Post-travel phone interviews were performed to assess health incidents during travel and individual responses of travellers to febrile illness. Results: Out of 714 patients who were monitored, 130 (18%) reported onset of fever during travel or 14 days after return. Of those travellers who reported fever, 100 (80%) carried SBET during travel. The vast majority of 79 (79%) febrile travellers who carried SBET did not seek medical assistance. Overall, 14 (14%) febrile patients who carried SBET and six (20%) patients who did not carry SBET took the correct measure (doctor visit or timely SBET administration) as a response to febrile illness, respectively. Only two travellers self-administered SBET, but both of them applied the wrong regimen. Conclusions: In view of declining malaria transmission and improving medical infrastructure in most countries of Southeast Asia and obvious obstacles concerning SBET as shown in this study the current strategy should be re-evaluated. Pre-travel advice concerning malaria in SEA should focus on appropriate mosquito bite protection and clearly emphasize the need to see a doctor within 24 h after onset of fever