Leishmania infantum leishmaniasis in corticosteroid – treated patients

BACKGROUND: The number of leishmaniasis cases associated with immunosuppression has increased regularly over the past 20 years. Immunosuppression related to HIV infection, immunosuppressive treatment, organ transplantation, and neoplastic diseases increases the risk for Leishmania-infected people to develop visceral illness. CASE PRESENTATION: Three cases of Leishmania infantum leishmaniasis in corticosteroid (CS)-treated patients are reported: an isolated lingual leishmaniasis in a farmer treated with CS for asthma, a severe visceral leishmaniasis associated with cutaneous lesions in a woman with myasthenia gravis, and a visceral involvement after cutaneous leishmaniasis in a man receiving CS. CONCLUSION: Physicians should recognise CS-treated patients as a population likely to be immunesuppressed. In immunodeficiency conditions, unusual forms of leishmaniasis can develop and foster the risk of a diagnostic delay and of poor response to therapy

Drug-Class Specific Impact of Antivirals on the Reproductive Capacity of HIV

Predictive markers linking drug efficacy to clinical outcome are a key component in the drug discovery and development process. In HIV infection, two different measures, viral load decay and phenotypic assays, are used to assess drug efficacy in vivo and in vitro. For the newly introduced class of integrase inhibitors, a huge discrepancy between these two measures of efficacy was observed. Hence, a thorough understanding of the relation between these two measures of drug efficacy is imperative for guiding future drug discovery and development activities in HIV. In this article, we developed a novel viral dynamics model, which allows for a mechanistic integration of the mode of action of all approved drugs and drugs in late clinical trials. Subsequently, we established a link between in vivo and in vitro measures of drug efficacy, and extract important determinants of drug efficacy in vivo. The analysis is based on a new quantity—the reproductive capacity—that represents in mathematical terms the in vivo analog of the read-out of a phenotypic assay. Our results suggest a drug-class specific impact of antivirals on the total amount of viral replication. Moreover, we showed that the (drug-)target half life, dominated by immune-system related clearance processes, is a key characteristic that affects both the emergence of resistance as well as the in vitro–in vivo correlation of efficacy measures in HIV treatment. We found that protease- and maturation inhibitors, due to their target half-life, decrease the total amount of viral replication and the emergence of resistance most efficiently

Anormalidades de fluxo sangüíneo cerebral em indivíduos dependentes de cocaína Cerebral blood flow abnormalities in cocaine dependent subjects

INTRODUÇÃO: Nos últimos anos, tem havido relatos de anormalidades do fluxo sanguíneo cerebral em indivíduos com o abuso de cocaína, detectadas por meio de tomografia computadorizada por emissão de fóton único (SPECT). Esse padrão anormal de perfusão cerebral tem sido associado a prejuízos cognitivos mas não a alterações observáveis por meio de exames de neuroimagem estrutural. Um problema envolvendo a maioria dos trabalhos publicados sobre esse tema é a inclusão de um grande número de usuários de heroína nas amostras estudadas. Essa outra droga também parece afetar o padrão de perfusão cerebral, particularmente durante estados de abstinência. MÉTODOS: Quatorze pacientes dependentes de cocaína (nenhum com uso de opióides) e 14 voluntários normais (grupo controle) foram submetidos a exames de SPECT com dímero de etil-cisteína marcado com tecnécio-99m. A análise dos exames de SPECT foi realizada por meio de análise visual qualitativa das imagens obtidas (procedimento padrão na prática clínica), realizada por um radiologista não informado sobre o diagnóstico dos indivíduos avaliados. RESULTADOS: A análise visual revelou um padrão sugestivo de irregularidades do fluxo sangüíneo cerebral em nove pacientes, mas em apenas dois controles (p = 0,018; teste exato de Fisher bicaudal). CONCLUSÕES: Anormalidades de circulação cerebral podem ter relação com prejuízos cognitivos relatados em populações de dependentes de cocaína. Embora déficits de perfusão cerebral associados ao uso de cocaína possam ser irreversíveis, têm surgido relatos na literatura de tratamentos para essas anormalidades de fluxo sangüíneo. Alterações de fluxo sangüíneo cerebral associadas à dependência de cocaína ocorrem mesmo na ausência de abuso ou dependência de opióides.<br>INTRODUCTION: In the last years, there have been reports of abnormalities in brain blood flow of cocaine abusers, detected by single photon computed emission tomography (SPECT). This abnormal pattern of brain perfusion has been associated with cognitive impairments but not with changes that could be seen by the use of structural neuroimaging techniques. One of the problems with most of the published papers on the subject is the inclusion of a large number of heroin users in the studied samples. Heroin also seems to affect the pattern of brain perfusion, particularly during withdrawal states. METHODS: Fourteen cocaine-dependent inpatients (none of them under the use of opiates) and 14 healthy volunteers (control group) were submitted to 99m-technetium ethyl-cysteinate dimer SPECT. The analysis of SPECT exams was made by visual qualitative analysis of the reconstructed images (standard method in clinical practice), performed by a radiologist unaware of the subjects' diagnoses. RESULTS: Visual analysis showed a pattern suggestive of irregularities in the cerebral blood flow in nine patients, but in only two controls (p = 0.018; two tailed Fisher's exact test). CONCLUSIONS: Abnormal brain circulation may be related to cognitive impairments reported in cocaine dependent subjects. Although brain perfusion deficits associated with cocaine use may be irreversible, there have been reports in the literature of treatments for these blood flow changes. There are abnormalities in the cerebral blood flow associated with cocaine dependence even in the absence of opiate abuse or dependence

Genetically diverse Plasmodium falciparum infections, within-host competition and symptomatic malaria in humans

International audienceThere is a large genetic diversity of Plasmodium falciparum strains that infect people causing diverse malaria symptoms. This study was carried out to explore the effect of mixed-strain infections and the extent to which some specific P. falciparum variants are associated with particular malaria symptoms. P. falciparum isolates collected during pharmacovigilance study in Nanoro, Burkina Faso were used to determine allelic variation in two polymorphic antigens of the merozoite surface (msp1 and msp2). Overall, parasite density did not increase with additional strains, suggesting the existence of within-host competition. Parasite density was influenced by msp1 allelic families with highest parasitaemia observed in MAD20 allelic family. However, when in mixed infections with allelic family K1, MAD20 could not grow to the same levels as it would alone, suggesting competitive suppression in these mixed infections. Host age was associated with parasite density. Overall, older patients exhibited lower parasite densities than younger patients, but this effect varied with the genetic composition of the isolates for the msp1 gene. There was no effect of msp1 and msp2 allelic family variation on body temperature. Haemoglobin level was influenced by msp2 family with patients harboring the FC27 allele showing lower haemoglobin level than mono-infected individuals by the 3D7 allele. This study provides evidence that P. falciparum genetic diversity influenced the severity of particular malaria symptoms and supports the existence of within-host competition in genetically diverse P. falciparum