29 research outputs found

    A systematic review of the clinical presentation, treatment and relapse characteristics of human Plasmodium ovale malaria

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    Additional file 1. Alphabetic list of included articles with overall quality of reporting and risk of bias assessment. -, not determined; overall risk of bias was declared “high” for case reports and case series; for applicable trials, overall risk of bias results from the detailed risk of bias assessment outlined in the Additional file 2; detailed completeness of reporting assessment is displayed in the Additional file 3

    In vitro activity of immunosuppressive drugs against Plasmodium falciparum

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    Background Solid organ transplant recipients are particularly vulnerable for infectious diseases due to prolonged immunosuppressive treatment. Residents of endemic regions and travellers may be exposed to malaria and may, therefore, require prolonged antimalarial chemoprophylaxis. The hypothesis of this study was that certain immunosuppressive drugs may exert clinically relevant anti- malarial activity. It was therefore designed to assess the intrinsic anti- malarial activity of everolimus, mycophenolic acid, and rapamycin against Plasmodium falciparum in an in vitro model. Methods Three laboratory adapted clones of P. falciparum and two isolates were used to assess the potential of mycophenolic acid, rapamycin and everolimus to inhibit in vitro growth of P. falciparum. The standard histidine rich protein 2 assay was employed and inhibitory drug concentrations (IC) were computed by non-linear regression analysis. Results All drugs were associated with complete inhibition of P. falciparum growth in in vitro assays. Mycophenolic acid demonstrated IC50 and IC90 values of 5.4 μmol/L and 15.3 μmol/L. Rapamycin inhibited P. falciparum growth at 7.2 μmol/L (IC50) and 12.5 μmol/L (IC90), respectively. Finally, everolimus displayed IC50 and IC90 values of 6.2 μmol/L and 11.5 μmol/L. There was no difference in in vitro activity against chloroquine sensitive or chloroquine resistant parasites. Conclusions All immunosuppressive drugs evaluated in this in vitro study demonstrated activity against P. falciparum. Inhibitory concentrations of mycophenolic acid are within clinically achievable plasma concentrations when used in solid organ transplant recipients. Further in vivo evaluation of mycophenolic acid either alone or in combination regimens may prove promising for the concomitant prevention of P. falciparum in solid organ transplant recipients living or travelling in malaria endemic regions

    Outbreak of Crimean-Congo haemorrhagic fever with atypical clinical presentation in the Karak District of Khyber Pakhtunkhwa, Pakistan

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    Abstract Background Crimean-Congo haemorrhagic fever (CCHF) is a potentially fatal disease endemic in Pakistan. The causative virus is transmitted by the bite of Hyalomma ticks or by contact with infected blood or tissue. First cases of the disease were reported in Pakistan in 1976 but regular outbreaks have been observed since the year 2000. A huge agricultural base with more than 175 million livestock, the concomitant presence of Hyalomma ticks and a lack of precautionary measures to prevent transmission lead to a considerable risk for exposed populations to contract CCHF in Pakistan. At the same time, secondary cases contracted by nosocomial transmission are reported from hospitals. Case presentation Here we present an outbreak of CCHF with four of six patients succumbing to the disease before the suspicion for CCHF was raised. Importantly, the main clinical features of these cases were gastrointestinal symptoms without any clinical signs of bleeding. Only the last two patients in this outbreak presented with typical signs of bleeding disorder and were then confirmed being infected by CCHF. Confirmation of diagnosis was done at the National Institute of Health by real-time RT-PCR. Conclusions This case series highlights the importance of early clinical suspicion for CCHF in exposed individuals and the need for improved precautionary measures against the spread of CCHF within the Pakistani population and hospitals

    Dalbavancin for treatment of implant-related methicillin-resistant Staphylococcus aureus osteomyelitis in an experimental rat model

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    Dalbavancin is a new semisynthetic lipoglycopeptide with improved antimicrobial activity against various gram-positive pathogens. It demonstrates an extensive plasma half-life which permits outpatient parenteral antimicrobial therapy with weekly intervals and might therefore be an excellent treatment alternative for patients requiring prolonged antimicrobial therapy. The present study investigated dalbavancin monotherapy in an experimental implant-related methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis model. A clinical MRSA isolate and a Kirschner-wire were inserted into the proximal tibia of anaesthetized Sprague-Dawley rats. Four weeks after infection 34 animals were treated over 4 weeks with either dalbavancin (20mg/kg loading-dose; 10mg/kg daily), vancomycin (50mg/kg twice daily) or left untreated. Twenty-four hours after the last treatment dose tibial bones and Kirschner-wires were harvested for microbiological examination. Based on quantitative bacterial cultures of osseous tissue, dalbavancin was as effective as vancomycin and both were superior to no treatment. No emergence of an induced glycopeptide-/lipoglycopeptide- resistance was observed after a treatment period of four weeks with either dalbavancin or vancomycin. In conclusion, monotherapy with dalbavancin was shown to be as effective as vancomycin for treatment of experimental implant-related MRSA osteomyelitis in rats, but both antimicrobials demonstrated only limited efficacy. Further studies are warranted to evaluate the clinical efficacy of dalbavancin for the treatment of periprosthetic S. aureus infections.(VLID)464184

    Molecular evidence for relapse of an imported Plasmodium ovale wallikeri infection

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    Abstract Background Malaria caused by Plasmodium ovale spp. has been neglected by and large from research and has received only little scientific attention during the past decades. Ovale malaria is considered to feature relapses by liver hypnozoites although scientific evidence for this paradigm is scarce. Case presentation Here, the case of a 16-year-old male, who presented with fevers to the outpatient department in Vienna, Austria, after travelling to Uganda and Papua New Guinea is described. Infection with Plasmodium malariae was diagnosed by microscopy and the patient was treated accordingly with a full course of supervised artemether–lumefantrine. He was discharged in good clinical condition with a negative blood smear. One month after initial diagnosis, he returned complaining of fever. Thick blood smear was positive again for malaria parasites, which were confirmed as P. ovale wallikeri by PCR. Retrospective analysis revealed the identical Plasmodium spp. in the initial blood samples. Molecular analysis of various gene loci (nuclear porbp2, 18S rRNA and potra genes) gave identical results providing further evidence for relapse by an identical parasite genotype. Consecutively, the patient was retreated with artemether–lumefantrine and received a regimen of primaquine according to WHO guidelines. Conclusion Conclusive evidence for relapses with P. ovale spp. is rare. The presented case provides convincing confirmation for the relapse paradigm based on re-appearing parasitaemia following supervised treatment in a non-endemic region with a parasite strain of identical genotype
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