Biofilm Dairy Foods Review: Effect of biofilm production on antimicrobial susceptibility of Staphylococcus aureus bovine mastitis strains from the most prevalent Canadian spa types.

Staphylococcus aureus intramammary infections often leads to clinical and subclinical mastitis in dairy cattle. Prediction of disease evolution and treatment efficacy based on the characteristics of disease-causing strains of S. aureus would significantly improve management of dairy herds. To study the impact of biofilm production and the influence of genetic lineage, we selected S. aureus isolates from the most prevalent Canadian spa types associated with bovine mastitis. Antimicrobial susceptibility in planktonic growth and for bacteria embedded in biofilm was compared. PCR was used to detect the bap gene responsible for atypical biofilm formation. All Canadian spa types from dairy cattle were susceptible to the 8 antimicrobial agents tested. Only strain sa3493 from spa type t267 showed a resistance to pirlimycin. However, bacteria producing larger amounts of biofilms better survived the bactericidal action of antimicrobial agents even when exposed to concentrations 64 folds higher than the minimal inhibitory concentration determined for planktonic cultures. Pirlimycin was more effective on bacteria producing low to moderate levels of biofilm compared with vancomycin or ceftiofur. Antimicrobial agents did not affect the viability of spa types t13401 and t605 that were high biofilm producers. While both these spa types produced high amounts of biofilm, only t605 possessed the bap gene. We also found a close relationship between DIM at sampling and the presence of spa type t605 isolates. These results suggest that detection of S. aureus spa type may help predict the effectiveness of antimicrobial therapy and that some spa types are more likely to be retrieved toward the end of the lactation.

[Spectrum of opportunistic fungal lung co-infections in COVID-19: What the radiologist needs to know]. / Espectro de coinfecciones pulmonares fúngicas oportunistas en COVID-19: lo que el radiólogo debe saber.

Fungal lung co-infections associated with COVID-19 may occur in severely ill patients or those with underlying co-morbidities, and immunosuppression. The most common invasive fungal infections are caused by aspergillosis, mucormycosis, pneumocystis, cryptococcus, and candida. Radiologists integrate the clinical disease features with the CT pattern-based approach and play a crucial role in identifying these co-infections in COVID-19 to assist clinicians to make a confident diagnosis, initiate treatment and prevent complications.

Uveitis and optic perineuritis in the context of myelin oligodendrocyte glycoprotein antibody seropositivity.

BACKGROUND AND PURPOSE: Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been identified in both children and adults with demyelination, with a strong association with bilateral or recurrent optic neuritis (ON). However, the full clinical spectrum of this newly described condition is unknown. We sought to describe non-ON inflammatory ophthalmological presentations such as uveitis and optic perineuritis in the context of MOG antibody seropositivity. METHODS: Using a live cell-based assay analysed by flow cytometry, we identified seropositive patients referred for MOG antibody testing in Australasia between 2014 and 2017. We identified four MOG antibody-positive patients with non-ON inflammatory ophthalmological presentations and present their detailed clinical information in this case series. RESULTS: Three patients had uveitis either in association with, or remote from, ON. One patient had optic perineuritis and peripheral ulcerative keratitis. We describe the presentation, examination, investigation findings and clinical course of these four patients. CONCLUSIONS: Recognition of these novel clinical associations may expand the clinical spectrum of MOG antibody-associated presentations. An expedited diagnosis may guide the management of these complex patients.

Coronary Artery Disease-Reporting and Data System (CAD-RADS): strengths and limitations.

A new standardised reporting system was introduced recently for coronary computed tomography (CT) angiography interpretation called CAD-RADS (Coronary Artery Disease-Reporting and Data System). Like any other new reporting platform, CAD-RADS has both advantages and disadvantages. Consistency in reporting, better clarity of communication, and more streamlined clinical recommendations are the major strengths of CAD-RADS. It has many limitations such as misinterpretation of CT angiography findings inherent to any CT angiography examination and unique disadvantages like misclassification of abnormalities, potential to misguide the referring physicians by suggesting management based on a single score. In addition, CAD-RADS does not include the details on location and extent of disease in the coronary arteries, coronary anomalies and other cardiac and extra cardiac findings.

Biofilm inhibitory efficiency of phytol in combination with cefotaxime against nosocomial pathogen Acinetobacter baumannii.

AIMS: This study aimed to evaluate the antibiofilm potential of phytol and cefotaxime combinations (PCCs) against Acinetobacter baumannii and to elucidate the molecular mechanism of their antibiofilm potential through the transcriptomic approach. METHODS AND RESULTS: Phytol and cefotaxime combination(s) (PCC(s) [160 µg ml-1  + 8 µg ml-1 for microbial type culture collection (MTCC) strain and 160 µg ml-1  + 0.5 µg ml-1 for clinical isolate] effectively inhibited the A. baumannii biofilm formation. Additionally, light, confocal laser scanning and scanning electron microscopic analyses validated the antibiofilm potential of PCCs. Furthermore, PCCs treated A. baumannii cells showed a decreased level of hydrophobicity index compared to their respective controls. Fourier-transform infrared (FT-IR) spectra of exopolysaccharide matrix extracted from PCCs-treated A. baumannii cells showed a visible decrease in absorbance of polysaccharides, nucleic acids and protein regions compared to the spectra of untreated controls. In the blood sensitivity assay, the PCCs-treated A. baumannii plates showed reduced a number of bacterial colonies compared to their control plates. Reduced level of catalase production was also observed in the PCCs treatment compared to their controls. Transcriptomic analysis revealed the downregulation of bfmR, bap, csuA/B, ompA, pgaA, pgaC and katE biofilm virulence genes in both the A. baumannii strains on treatment with PCCs. CONCLUSION: The obtained results of this study indicate that PCCs have potent antibiofilm activity and downregulate the biofilm-related virulence genes expression in A. baumannii. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this is the pioneering study, which shows the antibiofilm effect of PCCs against A. baumannii along with their molecular mechanism. The antibiofilm effect of PCCs could be a successful strategy for eradicating infections related to A. baumannii biofilms in nosocomial settings.

Phytosynthesized silver nanoparticles as antiquorum sensing and antibiofilm agent against the nosocomial pathogen Serratia marcescens: an in vitro study.

AIM: Serratia marcescens is an important multidrug-resistant human pathogen. The pathogenicity of S. marcescens mainly depends on the quorum sensing (QS) mechanism, which regulates the virulence factors production and biofilm formation. Hence, targeting QS mechanism in S. marcescens will ultimately pave the way to combat its pathogenicity. Thus, the present study is intended to evaluate the efficacy of Vetiveria zizanioides root extract-mediated silver nanoparticles (AgNPs) as a potent anti-QS and antibiofilm agent against S. marcescens. METHODS AND RESULTS: The AgNPs were synthesized using V. zizanioides aqueous root extract and the physiochemical properties of V. zizanioides-based AgNPs (VzAgNPs) were evaluated using analytical techniques such as ultraviolet-visible absorption spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, dynamic light scattering and scanning and transmission electron microscopic techniques. VzAgNPs were found to attenuate the QS-dependent virulence factors, namely prodigiosin, protease, lipase, exopolysaccharide productions and biofilm formation of S. marcescens, without inhibiting its growth. Further, the transcriptomic analysis confirmed the down-regulation of QS-dependent genes, which encode for the production of virulence factors and biofilm formation. CONCLUSION: The current study confirms VzAgNPs as an ideal anti-QS and antibiofilm agent against S. marcescens. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first approach that validates the anti-QS and antibiofilm potential of phytosynthesized VzAgNPs against the nosocomial pathogen, S. marcescens. As VzAgNPs exhibits potent antivirulent activities, it could be used to treat hospital-acquired S. marcescens infections.

Familial transient financial difficulties during infancy and long-term developmental concerns.

BACKGROUND: Socioeconomic difficulties affect the cognitive and emotional development of children. However, the focus of prior studies has largely been on poverty and material hardship. This study expands on the existing literature by examining the impact of familial transient financial difficulties during infancy on long-term cognitive and behavioral outcomes. METHODS: The National Longitudinal Surveys of Youth (79) were used to assess the association between a transient drop in family income by 50% or more (called transient income decline or TID) during the first 3 years of life and later-life Peabody Individual Achievement Math and Reading scores and behavior problem index (BPI) scores (N = 8272-17 348; median assessment age = 9 years). A subsample of matched siblings (N = 2049-4238) was examined to tease out maternal and intra-familial effects. RESULTS: Exposure to TID predicted increased total and externalizing BPI scores (std. coefficients of 0.10 and 0.09, respectively, p < 0.01) in the overall sample. Among matched siblings, exposure to TID predicted increased total, externalizing, and internalizing BPI scores (std. coefficients of 0.27, 0.25, and 0.23, respectively, p < 0.01). CONCLUSION: Familial transient financial difficulties can have long-lasting behavioral effects for infants. The study identifies an early risk factor and at-risk children, thus providing insight into developing early intervention measures for infants to avoid long-term behavioral problems.

Risk factors for community-associated multidrug-resistant Pseudomonas aeruginosa in veterans with spinal cord injury and disorder: a retrospective cohort study.

STUDY DESIGN: Retrospective cohort studyObjectives:To identify independent risk factors associated with community-associated multidrug-resistant Psedomonas aeruginosa (MDRPA) in a population of veterans with spinal cord injury and disorders (SCI/D). SETTING: A total of 127 Veterans Affairs healthcare facilities. METHODS: Laboratory results from 1 January 2012 to 31 December 2013 were collected, and MDRPA cultures were compared with non-MDRPA cultures. RESULTS: One thousand four hundred forty-one cultures were collected from Veterans with SCI/D, including 227 cultures with MDRPA isolates. Characteristics associated with an increased odds of MDRPA include age 50-64 (adjusted odds ratio (aOR)=1.80, 95% confidence interval (CI)=1.13-2.87), MDRPA culture in the past 365 days (aOR=9.12, 95% CI=5.88-14.15) and carbapenem exposure in the past 90 days (aOR=2.56, 95% CI=1.35-4.87). In contrast, paraplegia was associated with a 53% decreased odds of MDRPA compared with those with tetraplegia (aOR=0.47, 95% CI=0.32-0.69). CONCLUSIONS: Risk factors for community-associated MDRPA include prior history of MDRPA and exposure to carbapenems. Awareness of these factors is important for targeted prevention and treatment of MDRPA in patients with SCI/D.

Bacterial susceptibility patterns in patients with spinal cord injury and disorder (SCI/D): an opportunity for customized stewardship tools.

STUDY DESIGN: Retrospective observational study of bacterial susceptibilities in Veterans with SCI/D as compared to a general patient population. OBJECTIVES: The purpose of this project was to evaluate the prevalence and susceptibility of bacteria isolated from spinal cord injury and disorder (SCI/D) patients as compared with a general patient population and determine whether a SCI/D-specific antibiogram, a report of bacterial susceptibilities used to guide empiric antibiotic selection, would be a useful stewardship tool. SETTING: Veterans Affairs Medical Center located in Cook county, IL, USA. METHODS: Microbiology reports from 1 October 2012 to 30 September 2013 were compiled into a SCI/D-specific antibiogram and compared to a non-SCI/D antibiogram. RESULTS: Persons with positive cultures and SCI/D were younger and had a higher Charlson Index as compared to non-SCI/D patients (P<0.0001 for both). Five thousand one hundred and thirty-one unique isolate cultures were evaluated (SCI/D=23.0%). Frequencies of pathogens isolated in SCI/D and non-SCI/D differed. Methicillin-resistant Staphylococcus aureus occurred more frequently in SCI/D (27.8% vs 55.4%; P<0.0001). Gram-negatives had generally lower susceptibilities in SCI/D and a higher frequency of organisms producing extended-spectrum Beta-lactamases (17.6% vs 5.0%; P<0.0001), carbapenem-resistant Enterobacteriaceae (2.4% vs 0.5%; P<0.0001), carbapenem resistance (7.6% vs 2.4%; P<0.0001) and isolates resistant to ⩾3 antibiotic classes (60.7% vs 28.0%; P=0.0001). CONCLUSION: Different pathogens with poorer susceptibilities are isolated in SCI/D. Thus an SCI/D-specific antibiogram reflective of resistance patterns in these patients may increase the appropriateness of empiric antibiotic selection. The frequency of multi-drug resistant organisms in cultures obtained from patients with SCI/D is worrisome.

Non-neoplastic hepatic vascular diseases: spectrum of CT and MRI appearances.

The unique dual blood supply of the liver makes it one of the common sites for various vascular neoplastic and non-neoplastic diseases. Increasing use of multiphase contrast-enhanced computed tomography (CT) and dynamic magnetic resonance imaging (MRI) has led to increased identification of numerous non-neoplastic vascular entities apart from already well-known neoplastic lesions. The objective of this review is to describe the causes and clinical features and to familiarize the reader with the key imaging features of various non-neoplastic vascular diseases affecting the liver. Non-neoplastic vascular diseases are classified broadly as those affecting the hepatic veins, portal veins, hepatic artery, intrahepatic shunts, and other miscellaneous conditions.

Motivational interviewing improves exclusive breastfeeding in an Australian randomised controlled trial.

AIM: To increase maintenance of breastfeeding through improved primary care support. METHOD: A cluster randomised controlled trial recruited 15 rural family doctor's offices and 330 women who were currently breastfeeding took part. Eight practices formed the intervention group (154 women) and seven formed the control group (176 women). The practice nurses who provided the intervention used a specially designed motivational flowchart to speak to the mothers when they brought their child for immunisation at 2, 4 and 6 months. The nurses also attended preparatory workshops on breastfeeding management, counselling skills, motivational interviewing and reflective practice and were given resources and support. Breastfeeding rates were measured at 4 and 6 months. RESULTS: Randomisation equally distributed all measured variables except prenatal intentions to rejoin employment within 12 months (70% intervention, 56% control, p < 0.05). After adjustment, the 4-month figures showed significantly higher rates of exclusive breastfeeding (OR 1.88; 95%CI 1.01-3.50; p = 0.047) and full breastfeeding (water/juice allowed) (OR 1.95; 95%CI 1.03-3.69; p = 0.04) in the intervention group. There were no differences at 6 months. CONCLUSION: A motivational interviewing intervention by primary care health professionals who have undertaken a replicable training programme is feasible and effective in increasing exclusive breastfeeding and full/predominant breastfeeding at 4 months.

The mysterious organ. Spectrum of focal lesions within the splenic parenchyma: cross-sectional imaging with emphasis on magnetic resonance imaging.

Incidental splenic lesions are frequently encountered at imaging performed for unrelated causes. Splenic cysts, hemangiomas, and lymphomatous involvement are the most frequently encountered entities. Computed tomography and sonography are commonly used for initial evaluation with magnetic resonance imaging reserved as a useful problem-solving tool for characterizing atypical and uncommon lesions. The value of magnetic resonance imaging lies in classifying these lesions as either benign or malignant by virtue of their signal-intensity characteristics on T1- and T2-weighted imaging and optimal depiction of internal hemorrhage. Dynamic contrast-enhanced sequences may improve the evaluation of focal splenic lesions and allow characterization of cysts, smaller hemangiomas, and hamartomas. Any atypical or unexplained imaging feature related to an incidental splenic lesion requires additional evaluation and/or follow-up. Occasionally, biopsy or splenectomy may be required for definitive assessment given that some of tumours may demonstrate uncertain biologic behavior.

Investigation of the interactions between methadone and elvitegravir-cobicistat in subjects receiving chronic methadone maintenance.

Interactions between HIV and opioid dependence therapies are known to occur. We sought to determine if such interactions occurred between methadone and elvitegravir boosted with cobicistat (EVG/COBI). We performed a within-subject open-label pharmacokinetic and pharmacodynamic study of 11 HIV-seronegative subjects stabilized on at least 2 weeks of methadone. Subjects underwent baseline and steady-state evaluation of the effect of elvitegravir 150 mg once a day (QD) boosted with 150 mg QD of cobicistat (EVG/COBI) on methadone pharmacokinetic parameters. Safety and pharmacodynamics were monitored throughout the study. Compared to baseline values, the R-methadone mean area under the concentration-time curve to the end of the dosing period (AUCtau) (5,550 versus 6,210 h · ng/ml) and mean maximum concentration of drug in serum (Cmax) (316 versus 337 ng/ml) did not significantly increase in the presence of EVG/COBI. Compared to baseline values, the S-methadone mean AUCtau (7,040 versus 7,540 h · ng/ml) and mean Cmax (446 versus 452 ng/ml) did not significantly increase in the presence of EVG/COBI. The AUCtau, Cmax, and Ctau of elvitegravir and cobicistat did not significantly differ from those of historical controls. Opioid withdrawal or overdose was not observed among subjects in this study. The addition of EVG/COBI to stabilized patients receiving methadone did not affect methadone pharmacokinetics and pharmacodynamics. These two agents can be safely coadministered.

Induction of autoimmune diabetes in non-obese diabetic mice requires interleukin-21-dependent activation of autoreactive CD8⁺ T cells.

Non-obese diabetic (NOD) mice lacking interleukin (IL)-21 or IL-21 receptor do not develop autoimmune type 1 diabetes (T1D). We have shown recently that IL-21 may promote activation of autoreactive CD8(+) T cells by increasing their antigen responsiveness. To investigate the role of IL-21 in activating diabetogenic CD8(+) T cells in the NOD mouse, we generated IL-21-deficient NOD mice expressing the highly pathogenic major histocompatibility complex (MHC) class-I-restricted 8.3 transgenic T cell receptor (TCR). IL-21 deficiency protected 8.3-NOD mice completely from T1D. CD8(+) T cells from the 8.3-NOD.Il21(-/-) mice showed decreased antigen-induced proliferation but displayed robust antigen-specific cytolytic activity and production of effector cytokines. IL-21-deficient 8.3 T cells underwent efficient homeostatic proliferation, and previous antigen stimulation enabled these cells to cause diabetes in NOD.Scid recipients. The 8.3 T cells that developed in an IL-21-deficient environment showed impaired antigen-specific proliferation in vivo even in IL-21-sufficient mice. These cells also showed impaired IL-2 production and Il2 gene transcription following antigen stimulation. However, IL-2 addition failed to reverse their impaired proliferation completely. These findings indicate that IL-21 is required for efficient initial activation of autoreactive CD8(+) T cells but is dispensable for the activated cells to develop effector functions and cause disease. Hence, therapeutic targeting of IL-21 in T1D may inhibit activation of naive autoreactive CD8(+) T cells, but may have to be combined with other strategies to inhibit already activated cells.

Interleukin-15 plays an essential role in the pathogenesis of autoimmune diabetes in the NOD mouse.

AIMS/HYPOTHESIS: IL-15, induced by innate immune stimuli, promotes rheumatoid arthritis and inflammatory bowel disease. However, its role in autoimmune type 1 diabetes is unclear. Our aim is to define the role of IL-15 in the pathogenesis of diabetes in the NOD mouse model. METHODS: We generated NOD.Il15(-/-) mice expressing a polyclonal repertoire of T cell antigen receptor (TCR) or a transgenic TCR and monitored diabetes onset and insulitis. NOD Scid.Il15(-/-) (full name NOD.CB17-Prkdc (scid)/NCrCrl) and NOD Scid.gamma (full name NOD.Cg-Prkdc(scid) Il2rg ( tm1Wjl )/SzJ) mice were used to distinguish the requirement for IL-15 signalling in CD8(+) T cells and antigen-presenting cells (APCs) to induce disease. We examined the effect of blocking IL-15 signalling on diabetes onset in NOD mice. RESULTS: At 7 months of age, more than 75% of the NOD Il15(-/-) female mice remained diabetes free compared with only 30% in the control group. Diabetes incidence was also decreased in 8.3-NOD (full name NOD Cg-Tg[TcraTcrbNY8.3]-1Pesa/DvsJ).Il15(-/-) mice expressing a highly pathogenic transgenic TCR on CD8(+) T cells. Adoptive transfer of splenocytes from diabetic NOD and 8.3-NOD donors induced disease in NOD Scid recipients but not in NOD Scid.Il15(-/-) or NOD Scid.gamma mice. Transient blockade of IL-15 signalling at the onset of insulitis prevented diabetes in NOD mice. CONCLUSIONS/INTERPRETATION: Our results show that IL-15 is needed for the initial activation of diabetogenic CD8(+) T cells as well as for sustaining the diabetogenic potential of antigen-stimulated cells, acting on both CD8(+) T cells and on APCs. Our findings demonstrate a critical role for IL-15 in the pathogenesis of autoimmune diabetes and suggest that IL-15 is a promising therapeutic target.

The use of adjusted ideal body weight for overweight patients undergoing HPC mobilisation for autologous transplantation.

Generally, patients' actual body weight (ABW) is used to calculate the number of CD34⁺ cells to be harvested for autologous haematopoietic progenitor cell (HPC) transplantation. In our institution, 'overweight' patients weighing at least 25% more than their ideal body weight (IBW) have their adjusted ideal body weight (AdjIBW) used for determination of blood volume to be processed to achieve a minimum target of CD34⁺ cells per kilogram, as well as CD34⁺ cell dosage calculation at transplant. AdjIBW is calculated as follows: AdjIBW = IBW + 0.25 × (actual weight - IBW). We have used AdjIBW for 65/153 patients who have had autologous HPC harvests, with a median AdjIBW of 69 kg (range, 50-110 kg). Median actual weight was 90 kg (range, 62-175 kg). Median volume of peripheral blood processed to achieve a minimum 2 × 106 CD34⁺ cells/kg for these patients was 13.2 L (range, 5-35 L), and the median CD34⁺ cells × 106/kg collected for AdjIBW was 6.3 (range, 1.7-33). For normal-weight patients (n = 88; median ABW, 75 kg; range, 49-98 kg), the corresponding median apheresis volume was 16 L (range, 7-24 L), and median CD34⁺ cells × 106/kg harvested was 4.5 (range, 1.4-15.9). In total, 35 in a total transplant cohort of 82 patients had AdjIBW used to determine CD34⁺ cell dose at time of transplant, with a median of 4.5 × 106/kg, (if their ABW was used in the calculation; 3.1 × 106/kg), compared to median dose of 3.2 × 106/kg ABW for the normal-weight patient cohort. All patients engrafted with no significant difference between median times to neutrophil and platelet engraftment for the overweight (13 and 15 days, respectively) compared with normal-weight (12 and 14 days, respectively) patient cohorts. We conclude that the use of AdjIBW is a useful tool for successful harvest and subsequent transplant for overweight patients, with no adverse effect on engraftment times.

Barriers to artificial intelligence implementation in radiology practice: What the radiologist needs to know.

Artificial Intelligence has the potential to disrupt the way clinical radiology is practiced globally. However, there are barriers that radiologists should be aware of prior to implementing Artificial Intelligence in daily practice. Barriers include regulatory compliance, ethical issues, data privacy, cybersecurity, AI training bias, and safe integration of AI into routine practice. In this article, we summarize the issues and the impact on clinical radiology.

Spectrum of opportunistic fungal lung co-infections in COVID-19: What the radiologist needs to know.

Fungal lung co-infections associated with COVID-19 may occur in severely ill patients or those with underlying co-morbidities, and immunosuppression. The most common invasive fungal infections are caused by aspergillosis, mucormycosis, pneumocystis, cryptococcus, and candida. Radiologists integrate the clinical disease features with the CT pattern-based approach and play a crucial role in identifying these co-infections in COVID-19 to assist clinicians to make a confident diagnosis, initiate treatment and prevent complications.

Effect of artesunate and mefloquine in combination on the Fridericia corrected QT intervals in Plasmodium falciparum infected adults from Thailand.

OBJECTIVE: To ascertain whether mefloquine (MQ) produces electrocardiogram (ECG) changes that could be a risk for Torsades de Pointe (TdP), a potentially malignant, ventricular tachyarrhythmia. METHODS: We measured the Fridericia corrected QT (QTcF) intervals on 12 lead ECGs on days (D) 0, 3, 7 in Plasmodium falciparum infected adults, treated with oral artesunate (AS) and MQ as a new fixed dose (n = 25) combination or loose tablets (n = 25) over 3 days. Target total doses were 12 mg/kg of AS and 24-25 mg/kg of MQ. MQ concentrations ([MQ]) were measured by HPLC. RESULTS: All ECG intervals were similar between drug arms and were combined for analysis. Mean QTcF values were 389 (D0), 407 (D3) and 399 (D7) ms (Ps < 0.003 vs. D0); corresponding heart rates and [MQ]s were 83, 67 and 73 beats/minute (Ps ≤ 0.0003 vs. D0) and 0, 3095 and 1721 ng/ml. One male patient (loose arm) had a D3 QTcF 504 ms (D0 406 ms, D7 433 ms). In the modelling of QTcF and JTcF from D0 to D7, significant effects were observed individually for [MQ], temperature and heart rate (HR). The MQ AUC(0-∞) was not a significant factor. Using a manual descending, model building approach to select variables, the HR was the only significant variable (P = 0.001) over time in the model that best explained the changes in the QTcF and JTcF intervals. CONCLUSIONS: In this small group of patients, slowing heart rates due to malaria resolution best explained the observed increases in the QTcF intervals.