Using Death Certificate Reports to Find Severe Leptospirosis Cases, Brazil

Severe leptospirosis with pulmonary hemorrhage is emerging globally. Measures to control leptospirosis through sanitation depend on accurate case finding and reporting. Rapid death certificate reporting, plus necropsy of persons who died of leptospirosis, facilitates public health intervention and could provide an important tool in assessing the global burden of leptospirosis

Reversal of renal tubule transporter down-regulation during severe leptospirosis with antimicrobial therapy

A leptospirose é uma zoonose de importância mundial, causada por leptospiras patogênicas. Aproximadamente 5 a 10% das infecções humanas cursam com a forma grave. A Doença de Weil é a forma mais comum de doença grave e pode apresentarse com duas formas de evolução, aguda progressiva monofásica ou de curso prolongado. A doença grave se caracteriza por uma combinação de hemorragia, mais comumente pulmonar, icterícia e insuficiência renal, com letalidade de 5 a 15%. O rim é um órgão muito acometido na Leptospirose. Clinicamente o envolvimento renal ocorre de 16 a 40%, com manifestações peculiares como poliúria, hipocalemia, e perda de sódio. A disfunção tubular renal, é característica da leptospirose forma grave, com envolvimento dos transportadores renais de sódio ao longo do néfron, levando às manifestações observadas. A terapêutica antimicrobiana é recomendada na Leptospirose, porém com controvérsias à sua indicação após o quarto dia de doença. Quando da instalação da lesão não haveria benefícios com a utilização de antibióticos. O tratamento pode diminuir a morbidade e letalidade, assim como interferir no envolvimento renal e na expressão dos transportadores renais de sódio. A patogênese pode estar relacionada a efeitos diretos da leptospira ou a resposta inflamatória assim como o estresse oxidativo. A utilização de antioxidantes, pode ser considerada como terapia adjuvante. Nós avaliamos a expressão no túbulo proximal do trocador Na+-H+ (NHE3) e na porção espessa da medula ascendente o cotransportador Na+-K+-2Cl- (NKCC2), no modelo de hamster com as duas formas de evolução de doença grave, mimetizando a doença de humanos realizados em dois experimentos. Os experimentos envolveram animais infectados não tratados e tratados com ampicilina associado ou não ao antioxidante, N-acetilcisteína. A presença de antígenos de Leptospira e a expressão dos transportadores foram avaliadas por imunohistoquímica, e o ácido tiobarbitúrico, marcador de estresse oxidativo, (TBARS) foi quantificado.Hamsters infectados, apresentaram altas quantidades de antígenos nos tecidos-alvo, enquanto que a expressão de ambos os transportadores apresentou-se diminuída. O tratamento com ampicilina esteve associado com mínima detecção ou ausência de antígenos, restabelecimento da expressão dos transportadores nos respectivos locais e redução dos níveis de TBARS. O tratamento precoce e tardio com ampicilina restabeleceu os defeitos tubulares na leptospirose forma grave em ambos experimentos, sem benefícios com a utilização da N-acetilcisteína.Leptospirosis is a zoonosis of worldwide distribution. About 5-10% of all human infections presents with severe forms. Weil\'s syndrome, the most common presentation of severe forms of leptospirosis, may courses either as a single monophasic disease or as a disease with prolonged course, characterized by a combination of hemorrhage, particularly in the lung, renal failure, and jaundice, with fatality rates ranging from 5 to 15%. The kidney is an important target organ in leptospiral infection. Clinically, renal involvement in leptospirosis occurs in 16% to 40% of cases and is unique because of the atypical presentation of polyuria, hypokalemia, and sodium wasting, suggestive of a special form of tubular dysfunction related to the major renal sodium transporters expressed along the nephron. A wide range of antimicrobial therapy for leptospirosis was described and benefits have been disputed for cases with more than four days of clinical disease, because after a threshold of leptospiremia, the delayed use of antibiotics is unlikely to reduce fatality. Antimicrobial therapy is thought to interfere on fatality, renal involvement, and renal sodium transporters expression during severe disease. The pathogenesis may be related to direct effects of leptospiral compounds or inflammatory response due to oxidative stress. Antioxidant could be considered for adjunctive therapy.We evaluated the expression of proximal tubule type 3 Na+/H+ exchanger (NHE3) and thick ascending limb Na+-K+-2Cl- cotransporter (NKCC2) in infected non treated and treated hamsters reproducing the two forms of clinical human presentations of Weil\'s syndrome divided in two experiments. Animals were treated or not with ampicillin and/or N-acetyl-cysteine (NAC). Leptospiral antigen/s and expression of renal transporters were evaluated by immunohistochemistry, and serum thiobarbituric acid (TBARS) was quantified. Infected hamsters had high amounts of detectable leptospiral antigen/s in target tissues while renal expression of NHE3 and NKCC2 decreased. Ampicillin treatment was associated with minimal or no detection of leptospiral antigens, normal expression of NHE3 and NKCC2 transporters, and reduced levels of TBARS. Early and late ampicillin treatment rescued tubular defects in leptospirosis severe disease in both experiments, and there was no evidence of benefit from antioxidant therapy

A case report of clonidine induced syncope: a review of central actions of an old cardiovascular drug

Abstract Background Clonidine is an imidazoline sympatholytic, acting on both α2-adrenergic and imidazoline receptors in the brainstem to induce antihypertensive and negative chronotropic effects in the vasculature and heart respectively. Case presentation A 69-year-old gentleman with hypertension presented to the emergency department after multiple syncopal episodes over the past 12 months. Electrocardiogram demonstrated sinus bradycardia with a heart rate of 42 beats per minute. It was hypothesized that the antihypertensive agent clonidine was responsible for inducing symptomatic bradycardia. Clonidine was thus gradually tapered and then discontinued over five days restoring normal sinus rhythm rates while avoiding hypertensive rebound related to sympathetic surge. His heart rate and blood pressure remained within normal limits after the clonidine taper and subsequent adjustments to his other hypertensive medications and he was discharged. Conclusions While clonidine has fallen out of favor for its indication as an antihypertensive, it remains a viable option for the use of opioid withdrawal, chronic pain, and smoking cessation, necessitating the appropriate clinical and pharmacological competencies for a physician to prescribe. A discussion of the clinical effects of clonidine brainstem receptor activation follows

Microbiology of diabetic foot infections: from Louis Pasteur to 'crime scene investigation'

Were he alive today, would Louis Pasteur still champion culture methods he pioneered over 150 years ago for identifying bacterial pathogens? Or, might he suggest that new molecular techniques may prove a better way forward for quickly detecting the true microbial diversity of wounds? As modern clinicians faced with treating complex patients with diabetic foot infections (DFI), should we still request venerated and familiar culture and sensitivity methods, or is it time to ask for newer molecular tests, such as 16S rRNA gene sequencing? Or, are molecular techniques as yet too experimental, non-specific and expensive for current clinical use? While molecular techniques help us to identify more microorganisms from a DFI, can they tell us ‘who done it?', that is, which are the causative pathogens and which are merely colonizers? Furthermore, can molecular techniques provide clinically relevant, rapid information on the virulence of wound isolates and their antibiotic sensitivities? We herein review current knowledge on the microbiology of DFI, from standard culture methods to the current era of rapid and comprehensive ‘crime scene investigation' (CSI) techniques.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]