Paradoxical reactions in Buruli ulcer after initiation of antibiotic therapy: Relationship to bacterial load.

BACKGROUND: We investigated the relationship between bacterial load in Buruli ulcer (BU) lesions and the development of paradoxical reaction following initiation of antibiotic treatment. METHODS: This was a longitudinal study involving BU patients from June 2013 to June 2017. Fine needle aspirates (FNA) and swab samples were obtained to establish the diagnosis of BU by PCR. Additional samples were obtained at baseline, during and after treatment (if the lesion had not healed) for microscopy, culture and combined 16S rRNA reverse transcriptase/ IS2404 qPCR assay. Patients were followed up at regular intervals until complete healing. RESULTS: Forty-seven of 354 patients (13%) with PCR confirmed BU had a PR, occurring between 2 and 42 (median 6) weeks after treatment initiation. The bacterial load, the proportion of patients with positive M. ulcerans culture (15/34 (44%) vs 29/119 (24%), p = 0.025) and the proportion with positive microscopy results (19/31 (61%) vs 28/90 (31%), p = 0.003) before initiation of treatment were significantly higher in the PR compared to the no PR group. Plaques (OR 5.12; 95% CI 2.26-11.61; p<0.001), oedematous (OR 4.23; 95% CI 1.43-12.5; p = 0.009) and category II lesions (OR 2.26; 95% CI 1.14-4.48; p = 0.02) were strongly associated with the occurrence of PR. The median time to complete healing (28 vs 13 weeks, p <0.001) was significantly longer in the PR group. CONCLUSIONS: Buruli ulcer patients who develop PR are characterized by high bacterial load in lesion samples taken at baseline and a higher rate of positive M. ulcerans culture. Occurrence of a PR was associated with delayed healing. TRIAL REGISTRATION: ClinicalTrials.gov NCT02153034

Spectrophotometric determination of tizanidine and orphenadrine via ion pair complex formation using eosin Y

A simple, sensitive and rapid spectrophotometric method was developed and validated for the determination of two skeletal muscle relaxants namely, tizanidine hydrochloride (I) and orphenadrine citrate (II) in pharmaceutical formulations. The proposed method is based on the formation of a binary complex between the studied drugs and eosin Y in aqueous buffered medium (pH 3.5). Under the optimum conditions, the binary complex showed absorption maxima at 545 nm for tizanidine and 542 nm for orphenadrine. The calibration plots were rectilinear over concentration range of 0.5-8 μg/mL and 1-12 μg/mL with limits of detection of 0.1 μg/mL and 0.3 μg/mL for tizanidine and orphenadrine respectively. The different experimental parameters affecting the development and stability of the complex were studied and optimized. The method was successfully applied for determination of the studied drugs in their dosage forms; and to the content uniformity test of tizanidine in tablets

Recent updates and perspectives on approaches for the development of vaccines against visceral leishmaniasis

All rights reserved. Visceral leishmaniasis (VL) is one of the most important tropical diseases worldwide. Although chemotherapy has been widely used to treat this disease, problems related to the development of parasite resistance and side effects associated with the compounds used have been noted. Hence, alternative approaches for VL control are desirable. Some methods, such as vector control and culling of infected dogs, are insufficiently effective, with the latter not ethically recommended. The development of vaccines to prevent VL is a feasible and desirable measure for disease control, for example, some vaccines designed to protect dogs against VL have recently been brought to market. These vaccines are based on the combination of parasite fractions or recombinant proteins with adjuvants that are able to induce cellular immune responses, however, their partial efficacy and the absence of a vaccine to protect against human leishmaniasis underline the need for characterization of new vaccine candidates. This review presents recent advances in control measures for VL based on vaccine development, describing extensively studied antigens, as well as new antigenic proteins recently identified using immuno-proteomic techniquesThis work was supported by grants from Instituto Nacional de Ciência e Tecnologia em Nano-Biofarmacêutica, Rede Nanobiotec/Brasil-Universidade Federal de Uberlândia/CAPES, PRONEX-FAPEMIG (APQ-01019-09), FAPEMIG (CBB-APQ-00819-12 and CBB-APQ-01778-2014), and CNPq (APQ-482976/2012-8, APQ-488237/2013-0, and APQ-467640/2014-9). EAFC and LRG are recipients of the grant from CNPq. MACF is the recipient of grants from FAPEMIG/CAPE

Field deployment of loop-mediated isothermal amplification for centralized mass-screening of asymptomatic malaria in Zanzibar: a pre-elimination setting.

BACKGROUND: Molecular tools for detection of low-density asymptomatic Plasmodium infections are needed in malaria elimination efforts. This study reports results from the hitherto largest implementation of loop-mediated isothermal amplification (LAMP) for centralized mass screening of asymptomatic malaria in Zanzibar. METHODS: Healthy individuals present and willing to participate in randomly selected households in 60 villages throughout Zanzibar were screened for malaria by rapid diagnostic tests (RDT). In 50% of the study households, participants were asked to provide 60 μL of finger-prick blood for additional LAMP screening. LAMP was conducted in two centralized laboratories in Zanzibar, by trained technicians with limited or no previous experience of molecular methods. The LAMP assay was performed with Loopamp(TM) MALARIA Pan/Pf Detection Kit (Eiken Chemical Company, Japan). Samples positive for Plasmodium genus (Pan)-LAMP were re-tested using Plasmodium falciparum-specific LAMP kits. RESULTS: Paired RDT and LAMP samples were available from 3983 individuals. The prevalence of asymptomatic malaria was 0.5% (CI 95% 0.1-0.8) and 1.6% (CI 95% 1.1-2.2) by RDT and Pan-LAMP, respectively. LAMP detected 3.4 (CI 95% 2.2-5.2) times more Plasmodium positive samples than RDT. DNA contamination was experienced, but solved by repetitive decontamination of all equipment and reagents. CONCLUSIONS: LAMP is a simple and sensitive molecular tool, and has potential in active surveillance and mass-screening programmes for detection of low-density asymptomatic malaria in pre-elimination settings. However, in order to deploy LAMP more effectively in field settings, protocols may need to be adapted for processing larger numbers of samples. A higher throughput, affordable closed system would be ideal to avoid contamination

Sleep and Happiness in Urban-Dwelling Older Adults in Ghana: A Serial Multiple Mediation Model of Generalized Anxiety and Depressive Symptoms.

OBJECTIVE: Sleep problems (SP) are highly prevalent and seriously affect health and well-being in old age. The aim of this study was to examine the association between SP and happiness in an urban-dwelling older sample. The authors further explore the effects of generalized anxiety and depressive symptoms in the SP-happiness link using serial mediating modeling. METHODS: Data came from the 2016 to 2018 Aging, Health, Psychological Well-being, and Health-seeking Behavior Study in Ghana (n = 661). The authors measured happiness with the cross-culturally validated item on a five-point scale. The GAD-7 and the CESD-8, respectively, assessed generalized anxiety and depressive symptoms. Participants reported nighttime and daytime SP in the last 30 days. The SPSS-based Hayes' PROCESS macro program (Model 6) was constructed to quantify the hypothesized mediation effect. RESULTS: The analysis included 661 adults aged greater than or equal to 50 years (mean age = 65.53 [SD] = 11.89 years; 65.20% women). After full adjustment, path models showed that SP was negatively associated with happiness (β = -0.1277, 95%CI = -0.15950 to -0.096). Bootstrapping estimates revealed that the SP-happiness link was serially mediated via generalized anxiety representing 8.77%, depressive symptoms yielding 18.95%, and anxiety symptoms→depressive symptoms accounting for 26.70% of the total effect. CONCLUSION: Generalized anxiety and depressive symptoms may explain the negative association between SP and happiness in urban-dwelling older adults in the sub-Saharan African (SSA) context. Interventions, social and clinical, to improve happiness through sleep quality should include ways to improve mental health. Longitudinal and cross-cultural data are warranted to assess the bi-directionality of this relationship

Effect of amlodipine and lisinopril on microalbuminuria in patients with essential hypertension: A prospective study

Microalbuminuria can be present in 25–100% of patients with essential hypertension and is associated with increased incidence of cardiovascular events. Our goal was to evaluate the effect of a commonly used calcium channel blocker, amlodipine, and an angiotensin converting enzyme inhibitor, lisinopril on urinary albumin excretion in patients with mild to moderate essential hypertension. We screened 324 patients with essential hypertension for microalbuminuria and documented it in 120 patients. These 120 patients with microalbuminuria were randomly divided into two groups of 60 each, matched for age, sex, arterial pressure, creatinine clearance, and urinary albumin excretion so as to receive amlodipine or lisinopril. We prospectively measured their urinary albumin excretion and creatinine clearance prior to treatment and, four and eight weeks after treatment with amlodipine or lisinopril. Mean arterial pressure (mean ± SD) at baseline, after four weeks, and after eight weeks was 113.01 ± 4.38,104.93 ± 3.12, and 98.89 ± 1.75 mmHg (P < 0.0000); and 114.13 ± 7.11, 106.52 ± 3.50, and 100.89 ± 2.80 mmHg (P < 0.0000) in amlodipine and lisinopril groups, respectively. Urinary albumin excretion (mean ± SEM) at baseline, after four, and after eight weeks was 79.30 ± 3.74, 62.03 ± 3.61, and 52.02 ± 3.05 (P < 0.0000); and 73.96 ± 4.10, 72.39 ± 3.74, 66.12 ± 3.94 (P = 0.1742) in lisinopril and amlodipine groups, respectively. Lisinopril but not amlodipine, reduced the urinary albumin excretion significantly despite their similar antihypertensive efficacy. The clinical and prognostic significance of these observations need to be established