The changing landscape of infective endocarditis in South Africa

Background. Little is known about the current clinical profile and outcomes of patients with infective endocarditis (IE) in South Africa (SA). Objectives. To provide a contemporary and descriptive overview of IE in a representative SA tertiary centre. Methods. We conducted a retrospective review of the records of patients admitted to Groote Schuur Hospital, Cape Town, between 2009 and 2016 fulfilling universal criteria for definite or possible IE, in search of demographic, clinical, microbiological, echocardiographic, treatment and outcome information. Results. A total of 105 patients fulfilled the modified Duke criteria for IE. The median age of the cohort was 39 years (interquartile range (IQR) 29 - 51), with a male preponderance (61.9%). The majority of the patients (72.4%) had left-sided native valve endocarditis, 14.3% had right-sided disease, and 13.3% had prosthetic valve endocarditis. A third of the cohort had rheumatic heart disease. Although 41.1% of patients with left-sided disease had negative blood cultures, the three most common organisms cultured in this subgroup were Staphylococcus aureus (18.9%), Streptococcus spp. (16.7%) and Enterococcus spp. (6.7%). Participants with right-sided endocarditis were younger (29 years, IQR 27 - 37) and were mainly intravenous drug users (73.3%), and the majority cultured positive for S. aureus (73.3%) with frequent septic pulmonary complications (40.0%). The overall in-hospital mortality was 16.2%, with no deaths in the group with right-sided endocarditis. Predictors of death in our patients were heart failure (odds ratio (OR) 8.16, 95% confidence interval (CI) 1.77 - 37.70; p=0.007) and age >45 years (OR 4.73, 95% CI 1.11 - 20.14; p=0.036). Valve surgery was associated with a reduction in mortality (OR 0.09, 95% CI 0.02 - 0.43; p=0.001). Conclusions. IE remains an important clinical problem in a typical teaching tertiary care centre in SA. In this setting, it continues to affect mainly young people with post-inflammatory valve disease and congenital heart disease. The in-hospital mortality associated with IE remains high. Intravenous drug-associated endocarditis caused by S. aureus is an important IE subset, comprising ~10% of all cases, which was not reported 15 years ago, and culture-negative endocarditis remains highly prevalent. Heart failure in IE carries a significant risk of death and needs a more intensive level of care in hospital. Finally, cardiac surgery was associated with reduced mortality, with the largest impact in patients with heart failure

Efficacy of a series of alpha-pyrone derivatives against Leishmania (L. ) infantum and Trypanosoma cruzi

The neglected tropical diseases Chagas disease and leishmaniasis affect together more than 20 million people living mainly in developing countries. The mainstay of treatment is chemotherapy, however the drugs of choice, which include benznidazole and miltefosine, are toxic and have numerous side effects. Safe and effective therapies are urgently needed. Marine alpha-pyrones have been previously identified as scaffolds with potential antiprotozoan activities. In this work, using a phenotypic screen, twenty-seven examples of 3-substituted 4-hydroxy-6-methyl alpha-pyrones were synthesized and their antiparasitic efficacy evaluated against Leishmania (L.) infantum and Trypanosoma cruzi in order to evaluate structure-activity relationships within the series. The mechanism of action and the in vivo efficacy of the most selective compound against T. cruzi were evaluated using different techniques. In vitro data indicated that compounds 8, 15, 25, 26 and 28 presented IC50 values in the range between 13 and 54 µM against L. infantum intracellular amastigotes. Among them, hexanoyl substituted pyrone 8 was the most selective and potent, with a Selectivity Index (SI) > 14. Fifteen of the alpha-pyrones were effective against T. cruzi trypomastigotes, with 3-undecanoyl (11) and 3-tetradecanoyl (12) substituted pyrones being the most potent against trypomastigotes, with IC50 values of 1 and 2 µM, respectively, and SI higher than 70. Using flow cytometry and fluorescent-based assays, pyrone 12 was found to

As doenças tropicais negligenciadas A doença de Chagas e a leishmaniose afetam juntas mais de 20 milhões de pessoas que vivem principalmente nos países em desenvolvimento. O suporte principal do tratamento é a quimioterapia, no entanto, os medicamentos de escolha, que incluem benznidazol e miltefosina, são tóxicos e têm inúmeros efeitos colaterais. Terapias seguras e eficazes são urgentemente necessárias. As alfa-pironas marinhas foram previamente identificadas como andaimes com potenciais atividades antiprotozoárias. Neste trabalho, usando uma tela fenotípica, sintetizaram-se 27 exemplos de 4-hidroxi-6-metil alfa-pironas 3-substituídas e avaliou-se sua eficácia antiparasitária contra Leishmania (L.) infantum e Trypanosoma cruzi para avaliar a estrutura relações de atividade dentro da série. O mecanismo de ação e a eficácia in vivo do composto mais seletivo contra T. cruzi foram avaliados por diferentes técnicas. Dados in vitro indicaram que os compostos 8, 15, 25, 26 e 28 apresentaram valores de IC50 na faixa entre 13 e 54 µM contra amastigotas intracelulares de L. infantum. Entre elas, a pirona 8 substituída com hexanoílo foi a mais seletiva e potente, com um índice de seletividade (SI)> 14. Quinze das alfa-pironas foram eficazes contra as tripomastigotas de T. cruzi, com 3-undecanoil (11) e 3-tetradecanoil ( 12) pironas substituídas sendo as mais potentes contra tripomastigotas, com valores de IC50 de 1 e 2 µM, respectivamente, e SI superiores a 70. Usando citometria de fluxo e ensaios à base de fluorescência, a pirona 12 foi encontrada para