RESUMEN
We present case histories of four patients treated with artemether-lumefantrine for falciparum malaria in UK hospitals in 2015 to 2016. Each subsequently presented with recurrent symptoms and Plasmodium falciparum parasitemia within 6 weeks of treatment with no intervening travel to countries where malaria is endemic. Parasite isolates, all of African origin, harbored variants at some candidate resistance loci. No evidence of pfk13-mediated artemisinin resistance was found. Vigilance for signs of unsatisfactory antimalarial efficacy among imported cases of malaria is recommended.
Asunto(s)
Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Resistencia a Medicamentos/genética , Etanolaminas/uso terapéutico , Fluorenos/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Parasitemia/tratamiento farmacológico , Plasmodium falciparum/efectos de los fármacos , Proteínas Protozoarias/genética , África , Anciano , Combinación Arteméter y Lumefantrina , Combinación de Medicamentos , Femenino , Expresión Génica , Sitios Genéticos , Humanos , Malaria Falciparum/parasitología , Malaria Falciparum/patología , Masculino , Parasitemia/parasitología , Parasitemia/patología , Plasmodium falciparum/genética , Plasmodium falciparum/crecimiento & desarrollo , Recurrencia , Viaje , Insuficiencia del Tratamiento , Reino Unido , Adulto JovenRESUMEN
Cardiac myocyte dysfunction is clearly identified as underlying the acute heart failure associated with bacterial infection, as well as the chronic syndrome following cardiac damage, but the mechanisms leading to dysfunction in each case are not fully established. It is thought that local hormones such as endothelin 1 (ET-1) can increase the risk of heart failure in acute or chronic conditions. In the current study, we characterize myocytes as populations and identify a novel phenotype of the ventricular cardiac myocyte that does not contract appropriately on electrical stimulation. The noncontractile cardiac myocytes were viable and had normal calcium transients. The proportion of noncontractile cardiac myocytes was increased by bacteria (gram-positive Staphylococcus aureus or gram-negative Escherichia coli). Using selective ligands or myocytes from genetically modified mice, we established that the effects of S. aureus were mediated by Toll-like receptor 2/6 and of E. coli by Toll-like receptor 4. The transition to the noncontractile phenotype was strongly inhibited by ETA antagonism but unaffected by inhibition of NOS, suggesting that ET-1 and not NO mediates this phenomenon. These results are the first to describe the characteristics of this noncontractile phenotype and the mechanisms of its induction by bacteria. Description of the myocyte population, instead of effects only on individual cells, will be more relevant to the prediction of the depression of cardiac function.
Asunto(s)
Miocitos Cardíacos/metabolismo , Receptores Toll-Like/metabolismo , Animales , Atrasentán , Bacterias/crecimiento & desarrollo , Tamaño de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Antagonistas de los Receptores de Endotelina , Endotelina-1/genética , Endotelina-1/farmacología , Escherichia coli/crecimiento & desarrollo , Femenino , Expresión Génica/efectos de los fármacos , Isoproterenol/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/microbiología , Pirrolidinas/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Staphylococcus aureus/crecimiento & desarrollo , Receptores Toll-Like/genéticaRESUMEN
Old World species of Leishmania typically cause visceral and cutaneous leishmaniasis. Mucosal involvement is typically seen with infection by Leishmania species found in South America, usually after the healing of cutaneous leishmaniasis. We present five imported cases of mucosal leishmaniasis caused by Old World Mediterranean Leishmania infantum exclusively affecting the nasal mucosa or vocal cord. In only one case was there a recollection of a preceding cutaneous lesion compatible with cutaneous Leishmaniasis. Of significance was that four out of five cases were receiving local corticosteroids for chronic lung disorders and four were systemically immunosuppressed. This report highlights the importance of considering mucosal leishmaniasis in the differential diagnosis in those presenting with upper respiratory tract mucosal lesions with a relevant travel history to the Mediterranean and in whom malignancy has been excluded.
Asunto(s)
Leishmania infantum/aislamiento & purificación , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/parasitología , Anciano , Antiprotozoarios/uso terapéutico , Femenino , Humanos , Inmunosupresores , Leishmaniasis Visceral/tratamiento farmacológico , Londres/epidemiología , Masculino , Región Mediterránea/epidemiología , Persona de Mediana Edad , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapéutico , ViajeRESUMEN
Praziquantel is the mainstay of treatment of Schistosomiasis, which affects at least 262 million people worldwide. It is also used in the treatment of other trematode as well as cestode infections, with few safe and effective alternatives. It is generally well tolerated and allergic reactions are rare. In this report, we present a case of schistosomiasis with a history of a hypersensitivity reaction to praziquantel. Skin-prick and intradermal testing were performed, followed by treatment through rapid desensitization. This protocol may be of value to those patients requiring praziquantel treatment with a history of IgE-mediated allergy to the drug.
Asunto(s)
Desensibilización Inmunológica , Hipersensibilidad a las Drogas/diagnóstico , Praziquantel/uso terapéutico , Esquistosomiasis/tratamiento farmacológico , Adulto , Hipersensibilidad a las Drogas/tratamiento farmacológico , Femenino , Humanos , Inmunoglobulina E/sangre , Praziquantel/inmunología , Esquistosomiasis/inmunología , Reino UnidoRESUMEN
Our current knowledge of the clinical characteristics of enteric fever is drawn mainly from population-based studies in disease-endemic countries, and there are limited data published on cases in returning travelers. We report the clinical characteristics of enteric fever in 92 travelers returning to London, United Kingdom. Salmonella typhi and S. paratyphi resulted in an almost indistinguishable clinical picture. Rose spots and relative bradycardia were found only in a few patients. A total of 91% of the patients had a normal leukocyte count, which was associated with a markedly increased level of alanine aminotransferase in 82%. A total of 57% of the S. typhi isolates had decreased susceptibility to ciprofloxacin and resistance to nalidixic acid; these isolates were from southern Asia. Thirty percent were multidrug resistant; all were from southern Asia and Nigeria. None of the paratyphoid isolates were multidrug resistant but rates of decreased susceptibility to fluoroquinolones were higher than in S. typhi (74%).