Infectious diseases in German military personnel after predominantly tropical deployments: a retrospective assessment over 13 years.

OBJECTIVES: Military deployments to the tropics are associated with specific infection risks. To add to the available epidemiological information, infectious disease risks in German military personnel returning from predominantly tropical deployments were assessed. METHODS: Since 2006, German soldiers returning from predominantly tropical deployments have been offered the opportunity of returnee screenings at the Department of Tropical Medicine and Infectious Diseases of the Bundeswehr Hospital Hamburg. Case files and diagnostic results recorded between 2006 and 2018 were retrospectively assessed to identify deployment-associated infectious disease risks. RESULTS: Along with high enteric colonisation rates with apathogenic protozoa and resistant Enterobacteriaceae, direct or indirect proof of infections among the 764 assessed cases comprised Plasmodium spp (n=37), Giardia duodenalis (n=21), Schistosoma spp (n=14), Yersinia enterocolitica (n=5), Strongyloides stercoralis (n=3), Campylobacter jejuni (n=1), Leishmania spp (n=1) and Salmonella enterica (n=1), as well as latent infections with Mycobacterium tuberculosis complex (n=8). The infections were mainly imported from the African region and Eastern Mediterranean region and high proportions of cases lacked typical symptoms. Reported side effect rates of antimalarial chemoprophylaxis for mefloquine (n=121), atovaquone/proguanil (n=49) and doxycycline (n=6) were 36.3%, 19.3% and 11.8%, respectively, while non-compliance rates were 12.9%, 13.0% and 5.9%, respectively. CONCLUSIONS: Considerable rates of infections with sometimes atypical or absent symptoms confirm a need for returnee screenings after tropical deployments. High reported side effect rates for mefloquine support its replacement by atovaquone/proguanil or doxycycline for antimalarial chemoprophylaxis.

Loop-mediated isothermal amplification for paratyphoid fever - a proof-of-principle analysis.

In-house loop-mediated isothermal amplification (LAMP) procedures for the detection of paratyphoid fever-associated bacteria on serovar level were evaluated. Therefore, LAMP primers for Salmonella genus, for two LAMP schemes for S. Paratyphi A, for S. Paratyphi B and for S. Paratyphi C were tested with DNA from culture isolates from strain collections and spiked blood cultures against published PCR protocols targeting the same micro-organisms. Sensitivity and specificity for DNA from culture isolates verified by LAMP ranged from 80·0 to 100·0% and 96·1 to 100·0% vs 65 to 100% and 98·7 to 100% for the PCR approaches. For the spiked blood culture materials, sensitivity and specificity for LAMP ranged from 87·5 to 100·0% and 96·7 to 100·0% vs from 60 to 100% and 98·2 to 100% for PCR. In conclusion, LAMP for paratyphoid fever shows comparable performance characteristics as PCR. Due to its easy application, the procedure is well suited for surveillance purposes in resource-limited settings. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of easy-to-apply, point-of-care-testing-like loop-mediated isothermal amplification (LAMP) for the diagnosis of paratyphoid fever is evaluated. This approach can contribute to low-threshold availability of surveillance options for resource limited settings. Easy-to-teach and easy-to-apply LAMP schemes with similar performance characteristics as PCR are provided. The described test evaluation is of particular use for surveillance and public health experts.

[Sandfly fever-a "neglected" disease]. / Sandmückenfieber ­ eine "vernachlässigte" Krankheit.

A 45-year-old woman presented at the outpatient department of a center for tropical diseases with fever, diarrhea, headache, myalgia, malaise, and an itchy papular rash. She had been on holiday with her family for 11 days in a mountain village in northern Cyprus. The place was infested with a lot of small, stinging flies or mosquitoes. She and her family became sick after they returned home. The physical examination was normal apart from the rash on the inside of the extremities. Significantly elevated transaminases and a slightly increased C­reactive protein level were found in the blood examination. Considering the country of travel, the report of the "stinging flies" and the clinical presentation, sandfly fever was also taken into account as a differential diagnosis for the hepatitis. Antibodies to the sandfly fever Sicilian virus (SFSV) were detected. They showed the typical dynamics during the course of the illness and thus "pappataci fever" was diagnosed. The case report and a short review of up-to-date literature is meant encourage consideration of phlebovirus infection as a possible differential diagnosis in travelers or refugees suffering from severe febrile hepatitis and rash or aseptic viral meningitis after their stay in the Mediterranean area.

[Dengue fever : Symptoms, epidemiology, entomology, pathogen diagnosis and prevention]. / Denguefieber : Klinik, Epidemiologie, Entomologie, Erregerdiagnostik und Prävention.

Dengue infections are among the most frequent causes of febrile disease in tropical climates. Infections are caused by a flavivirus transmitted by the Aedes mosquito. Aedes aegypti mosquitos are the main transmitters of Dengue viruses. Since these insects are both diurnal and container breeders, particular prevention and control measures are required. Symptom severity varies and can range from a mild, flu-like clinical picture to severe hemorrhage and shock. The most common symptoms experienced by travelers include fever, muscular pain, headaches and skin rash. Depending on the stage of infection, either rapid point-of-care tests or-during the viraemic phase-direct molecular detection of pathogens can be used as diagnostic methods. Serological diagnosis is challenging in terms of interpretation due to serological cross reactions with other flaviviruses.

Geranylgeranyl diphosphate synthase: an emerging therapeutic target.

Proteins modified post-translationally by geranylgeranylation have been implicated in numerous cellular processes related to human disease. In recent years, the study of protein geranylgeranylation has advanced tremendously in both cellular and animal models. The advances in our understanding of the biological roles of geranylgeranylated proteins have been paralleled by advances in the medicinal chemistry of geranylgeranylation inhibitors such as those that target geranylgeranyl transferases I and II and geranylgeranyl diphosphate synthase (GGDPS). Although these findings provide the rationale for further development of geranylgeranylation as a therapeutic target, more advanced studies on the efficacy of this approach in various disease models will be required to support translation to clinical studies. This article attempts to describe the advances in (and the challenges of) validation of GGDPS as a novel therapeutic target and assesses the advantages of targeting GGDPS relative to other enzymes involved in geranylgeranylation.

2-(Acyloxy)ethylphosphonate analogues of prenyl pyrophosphates: synthesis and biological characterization.

2-(Acyloxy)ethylphosphonate analogues of geranyl, farnesyl, and geranylgeranyl pyrophosphate have been prepared. Horner-Wadsworth-Emmons condensation of different terpene aldehydes with an unsymmetrical bisphosphonate was the key step in syntheses of the phosphonates bearing alpha,beta-unsaturated acyloxy groups. After preparation of the respective phosphonic acids through reaction with TMSBr, both acids and esters were tested for their effects on DNA synthesis in human-derived myeloid and lymphoid leukemia cell lines. The phosphonate esters varied substantially in their ability to impair proliferation of the different cell lines, but testing against one possible target, farnesyl protein transferase (FPTase), revealed little impact at concentrations ranging up to 10 microM. Because the corresponding 2,3-dihydro compounds showed similar biological activity, conjugate addition would not appear to be involved in the toxicity.

Synthesis of phosphonate derivatives of uridine, cytidine, and cytosine arabinoside.

The vinyl phosphonate derivatives of uridine, cytidine, and cytosine arabinoside (ara-C) have been prepared through oxidation of appropriately protected nucleosides to the 5' aldehydes and Wittig condensation with [(diethoxyphosphinyl)methylidine]triphenylphosphorane. Dihydroxylation of these vinyl phosphonates with an AD-mix reagent generated the new 5',6'-dihydroxy-6'-phosphonates. After hydrolysis of the phosphonate esters and the various protecting groups, the six phosphonic acids were tested for their ability to serve as substrates for the enzyme nucleotide monophosphate kinase and for their toxicity to K562 cells.

Engineering novel cell surface receptors for virus-mediated gene transfer.

The absence of viral receptors is a major barrier to efficient gene transfer in many cells. To overcome this barrier, we developed an artificial receptor based on expression of a novel sugar. We fed cells an unnatural monosaccharide, a modified mannosamine that replaced the acetyl group with a levulinate group (ManLev). ManLev was metabolized and incorporated into cell-surface glycoconjugates. The synthetic sugar decorated the cell surface with a unique ketone group that served as a foundation on which we built an adenovirus receptor by covalently binding biotin hydrazide to the ketone. The artificial receptor enhanced adenoviral vector binding and gene transfer to cells that are relatively resistant to adenovirus infection. These data are the first to suggest the feasibility of a strategy that improves the efficiency of gene transfer by using the biosynthetic machinery of the cell to engineer novel sugars on the cell surface.

Phosphonate and bisphosphonate analogues of farnesyl pyrophosphate as potential inhibitors of farnesyl protein transferase.

Several phosphonate and bisphosphonate analogues of farnesyl pyrophosphate have been prepared for an examination of their ability to inhibit farnesyl protein transferase (FPTase). A Horner-Wadsworth-Emmons condensation of farnesal or geranial with tetraethyl methylenediphosphonate gave the desired vinyl phosphonates, while alkylation of the dimethyl methylphosphonate anion with a terpenoid bromide gave the corresponding saturated phosphonates. Alkylation of tetraethyl methylenediphosphonate with farnesyl bromide gave the expected alkyl bisphosphonate, which was converted to its alpha, beta-unsaturated derivative by preparation of the phenyl selenide, oxidation to the selenoxide, and elimination. In a similar fashion, triethyl phosphonoacetate was converted to a farnesyl pyrophosphate analogue by reaction with farnesyl bromide. After preparation of the respective acids, each compound was tested for inhibition of FPTase at concentrations ranging up to 10 microM. The effect of these compounds on FPTase activity varied substantially, ranging from depressed to surprisingly enhanced enzymatic activity.

Stereochemistry-dependent inhibition of RAS farnesylation by farnesyl phosphonic acids.

This investigation compares the effects of three farnesyl pyrophosphate analogs on selected aspects of isoprenoid metabolism. E,E-alpha-Hydroxyfarnesylphosphonate was prepared by an improved variation on a literature synthesis, which also gave access to the new Z,E-alpha-hydroxyfarnesyl- and alpha-hydroxygeranylphosphonates. A striking find is that only E,E-alpha-hydroxyfarnesylphosphonate induces alteration of RAS processing in intact human-derived leukemia cells and inhibits farnesyl protein transferase in enzyme assays, while the Z,E-alpha-farnesyl- and geranylphosphonates are inactive. The inhibitory activity of E,E-alpha-hydroxyfarnesylphosphonate is greater in enzyme than intact cell assays. This active compound does not significantly inhibit geranylgeranyl protein transferase I or squalene synthase, nor does it diminish cholesterol synthesis. These results indicate that the length of the terpenoid chain and olefin stereochemistry allow selective inhibition of critical enzymes of terpenoid metabolism. Discrimination was observed between inhibition of farnesyl protein transferase and squalene synthase by E,E-alpha-hydroxyfarnesylphosphonate, even though both enzymes utilize farnesyl pyrophosphate as their natural substrate.

Repair of defects of the nasal ala.

BACKGROUND: Alar defects present a reconstructive challenge. OBJECTIVE: To define closure options for alar defects of variable thickness and location. METHODS: The repair options for closure of alar defects are reviewed and discussed with regard to depth of defect and complexity of reconstruction. CONCLUSION: Surgeons repairing defects of the nose should develop a variety of reconstructive approaches for the ala including but not limited to those presented here.

(2'S,3'S,4'R)-5'-O-benzoyl-3'-deoxy-3' beta-diethylphosphono-2'-O-tert-butyldimethylsilyluridine.

3'-Hydroxy-3'-diethylphosphononucleosides readily undergo radical deoxygenation under modified Barton conditions to give two diastereomers of the parent diethyl phosphonate. However, the stereochemistry of the diastereomers is difficult to establish by spectral means. When the major product of one such reaction was obtained in crystalline form, a single crystal diffraction analysis was conducted on that diastereomer, the title compound, C26H39N2O9PSi.

The postauricular (revolving door) island pedicle flap revisited.

BACKGROUND: Few satisfactory closure options exist for large anterior auricular defects. OBJECTIVE: To describe the use of the postauricular (revolving door) island pedicle flap for closure of large defects on the scapha, antihelix, and helix. METHODS: Mohs micrographic surgery for excision of basal cell carcinoma was performed on the anterior auricular surface of two patients. Both defects were closed using a posterior auricular island flap that was advanced through cartilage with excellent cosmetic results. Other closure options are discussed for this region. CONCLUSION: The postauricular (revolving door) island pedicle flap is a good closure option for large anterior auricular defects lacking perichondrium and not easily repaired by other methods.

Cyclic (1R,3R)-1,3-dimethyltrimethylene [(5R)-2-hydroxy-5-methyl-5-(2- methyl-1,3-dioxolan-2-yl)-1-cyclohexen-1-yl]-phosphonate, a stable enol.

The title compound, C16H27O6P, was obtained from the rearrangement of the corresponding vinyl phosphate. 31P NMR experiments in solution have shown that this compound equilibrates to a mixture of three isomers in nearly equal proportions. In the crystalline state a single isomer is found which diffraction analysis identified as the enol form of the beta-keto phosphonate having R stereochemistry at atom C(8).

(1 beta, 5 alpha, 6 beta)-10,10- (1,2-ethylenedioxy)-1,5-dimethylbicyclo[4.4.0]decan-4-one.

The title compound (1) [alternative name: 5,8a-dimethyl(decahydronaphthalene)-1-spiro-2'-(1',3'-dioxolan+ ++)-6-one, C14H22O3] was obtained as the major product upon Pd/CaCO3-catalyzed hydrogenation of the corresponding enone (2). The analysis of the crystal structure of (1) has established that the monoacetal is cis-fused and that both rings adopt nearly perfect chair forms. The C(5) methyl group is in an alpha position, resulting directly from syn-hydrogenation of the enone. While there are two possible chair-chair conformations for cis-decalins, the title compound crystallized in the conformation which places the C(5) methyl group in an equatorial position.

Structure of a modified nucleoside, 3' alpha-diethylphosphono-3' beta-hydroxy-5'-O-tritylthymidine.

The modified nucleoside of the title was synthesized by nucleophilic addition of lithium diethyl phosphite to the corresponding 3'-keto nucleoside under basic conditions. C--P bond formation resulted from attack on the alpha face, trans to C(5') and the thymine ring. One molecule of EtOH crystallized with the nucleoside (C33H37N2O8P.-C2H6O). Intermolecular hydrogen bonds were observed between the O atom of the alcohol and the O(3')hydroxyl H atom, and between the phosphoryl O atom, O(5), and the N(3) H atom of the thymine ring.

Vidalols A and B, new anti-inflammatory bromophenols from the Caribbean marine red alga Vidalia obtusaloba.

Chemical studies of the Caribbean red alga Vidalia obtusaloba have resulted in the isolation of two new bromophenolic metabolites, vidalols A and B (1, 2). The new compounds were discovered as part of an organized effort to isolate new naturally-occurring anti-inflammatory agents with a focus upon those which may function through the inhibition of phospholipase A2.

Treatment of postoperative infection of ascending aorta and transverse aortic arch, including use of viable omentum and muscle flaps.

Postoperative infection of the ascending aorta and aortic arch in 40 patients was treated by antibiotic therapy alone (4 patients) or by operation and lifelong suppressive antibiotic therapy (36 patients). Complications of infection included antibiotic-resistant infection, infected false aneurysm, rupture of suture line, aortocutaneous fistulas, aortic-right ventricular fistulas, arterial embolus, aortic valve insufficiency, aortobronchial fistula, mediastinal abscess, and chest wall problems. These were treated by a variety of operations including composite valve-graft replacement, graft replacement, patch-graft closure of false aneurysm, simple suture of disrupted suture lines and false aneurysm, and debridement of mediastinum and chest wall. The area of reconstruction was covered, and mediastinal dead space was reduced by mobilization of viable tissue, including local tissue and distant structures such as flaps of muscle and omentum. Thirty-three patients (83%) were early survivors, and 28 patients (70%) were alive and well at last follow-up 4 months to 6.5 years after operation.