Antiarrhythmic and electrophysiologic effects of flecainide on acutely induced atrial fibrillation in healthy horses

BACKGROUND: Only few pharmacologic compounds have been validated for treatment of atrial fibrillation (AF) in horses. Studies investigating the utility and safety of flecainide to treat AF in horses have produced conflicting results, and the antiarrhythmic mechanisms of flecainide are not fully understood. OBJECTIVES: To study the potential of flecainide to terminate acutely induced AF of short duration (≥15 minutes), to examine flecainide‐induced changes in AF duration and AF vulnerability, and to investigate the in vivo effects of flecainide on right atrial effective refractory period, AF cycle length, and ventricular depolarization and repolarization. ANIMALS: Nine Standardbred horses. Eight received flecainide, 3 were used as time‐matched controls, 2 of which also received flecainide. METHODS: Prospective study. The antiarrhythmic and electrophysiologic effects of flecainide were based on 5 parameters: ability to terminate acute pacing‐induced AF (≥15 minutes), and drug‐induced changes in atrial effective refractory period, AF duration, AF vulnerability, and ventricular depolarization and repolarization times. Parameters were assessed at baseline and after flecainide by programmed electrical stimulation methods. RESULTS: Flecainide terminated all acutely induced AF episodes (n = 7); (AF duration, 21 ± 5 minutes) and significantly decreased the AF duration, but neither altered atrial effective refractory period nor AF vulnerability significantly. Ventricular repolarization time was prolonged between 8 and 20 minutes after initiation of flecainide infusion, but no ventricular arrhythmias were detected. CONCLUSIONS AND CLINICAL IMPORTANCE: Flecainide had clear antiarrhythmic properties in terminating acute pacing‐induced AF, but showed no protective properties against immediate reinduction of AF. Flecainide caused temporary prolongation in the ventricular repolarization, which may be a proarrhythmic effect

Case-control investigation of invasive Salmonella disease in Africa - comparison of human, animal and household environmental isolates find no evidence of environmental or animal reservoirs of invasive clades/strains

Background Invasive Salmonella infections cause significant morbidity and mortality in Sub-Saharan Africa. However, the routes of transmission are uncertain. We conducted a case-control study of index-case and geographically-matched control households in Blantyre, Malawi, sampling Salmonella isolates from index cases, healthy people, animals, and the household environment. Methodology Sixty index cases of human invasive Salmonella infection were recruited (March 2015-Oct 2016). Twenty-eight invasive Non-Typhoidal Salmonella (iNTS) disease and 32 typhoid patients consented to household sampling. Each index-case household was geographically matched to a control household. Extensive microbiological sampling included stool sampling from healthy household members, stool or rectal swabs from household-associated animals and boot-sock sampling of the household environment. Findings 1203 samples from 120 households, yielded 43 non-Typhoidal Salmonella (NTS) isolates from 25 households (overall sample positivity 3.6%). In the 28 iNTS patients, disease was caused by 3 STs of Salmonella Typhimurium, mainly ST313. In contrast, the isolates from households spanned 15 sequence types (STs). Two S . Typhimurium isolates from index cases closely matched isolates from their respective asymptomatic household members (2 and 3 SNP differences respectively). Despite the recovery of a diverse range of NTS, there was no overlap between the STs causing iNTS disease with any environmental or animal isolates. Conclusions The finding of NTS strains from index cases that matched household members, coupled with lack of related animal or environmental isolates, supports a hypothesis of human to human transmission of iNTS infections in the household. The breadth of NTS strains found in animals and the household environment demonstrated the robustness of NTS sampling and culture methodology, and suggests a diverse ecology of Salmonella in this setting. Healthy typhoid ( S . Typhi) carrier state was not detected. The lack of S . Typhi isolates from the household environment suggests that further methodological development is needed to culture S . Typhi from the environment. Author summary Invasive Salmonella infections cause the loss of millions of disability adjusted life years (DALYs) every year globally. The two main types of invasive Salmonella infections in Africa are i) typhoid fever, caused by Salmonella Typhi, and ii) invasive Non-Typhoidal Salmonella (iNTS) disease, primarily caused in our setting by Salmonella Typhimurium. Despite the high disease burden, and the observed differences between the epidemiology of typhoid and iNTS disease, we lack an understanding of the reservoirs and transmission routes of iNTS. Therefore, we carried out extensive microbiological sampling of the household members, domestic animals, and living environments of patients with invasive Salmonella infections, and of geographically-matched control households, and investigated the genetic relationships between household Salmonella and index-case blood-stream isolates by whole genome sequencing (WGS). We identified a wide range of NTS serovars / sequence types across all households and sample-types, but only identified Salmonella that matched iNTS that matched invasive cases strains in the stool of healthy people from the same households. Our findings support, but cannot prove, the hypothesis that iNTS-associated strains are transmitted from person-to-person. Boot-sock sampling of the household environment gave the highest yield of Salmonella of any of our sampling strategies. None of the 41 environmental Salmonella isolates from non-human sources, including 4 domestic animal-associated isolates, matched the disease-causing sequence types. Our findings are consistent with a hypothesis that the reservoir of Typhimurium iNTS infections is the human gastrointestinal tract, and transmission occurs within households. Longitudinal studies are required, however, to confirm this hypothesis