The efficacy of a whole foods, plant-based dietary lifestyle intervention for the treatment of peripheral neuropathic pain in leprosy: a randomized control trial protocol.

Introduction: Despite effective treatment of leprosy via WHO-approved multi-drug therapy (MDT), patients still suffer from debilitating neuropathic sequelae, including peripheral neuropathic pain (PNP), and continue to develop intercurrent etiologies (such as diabetes), and progressive existing neuropathy over time. Strategies seeking to improve physiological and metabolic wellness, including those that reduce systemic inflammation and enhance immune responsiveness to neurotoxic factors may influence underlying neuropathic etiologies. A whole food plant-based diet (WFPBD) has been shown to be effective in the management of neuropathic pain due to diabetes, limiting severity and relevant symptomology. Diabetes remains a significant sequela of leprosy, as up to 50% of patients in reaction requiring corticosteroids, may develop a biochemical diabetes. As nutritional interventions may modulate both leprosy and diabetes, a specific exploration of these relationships remains relevant. Objectives: (1) To demonstrate the effect of a WFPBD lifestyle intervention, on neuropathic pain variables in leprosy; and (2) To contextualize the significance of diet in the treatment of chronic sequelae in leprosy by evaluating tolerability and side effect profile. Methods: A prospective, randomized, controlled, single-blind, multicentre interventional trial is described. Weekly one-hour dietary counseling sessions promoting a WFPBD emphasizing vegetables, fruits, whole-grains, nuts, and legumes, omitting animal products, and limiting fat intake over a six-month duration will be implemented. Participants will be 70 age and sex-matched individuals experiencing active or treated "cured" leprosy and PNP, randomized to either intervention or control groups. Primary outcome measures include efficacy via visual analog scale, subjective questionnaire and objective quantitative sensory testing, as well as safety, tolerability, and harms of a WFPBD on PNP in leprosy. This study will be initiated after Research Ethics Board (REB) approval at all participating sites, and in advance of study initiation, the trial will be registered at ClinicalTrials.gov. Expected impact: It is hypothesized that WFPBDs will mitigate progression and severity of PNP and potentially reduce the adverse events related to standard corticosteroid treatment of leprosy reactions, thereby reducing disease severity. By examining the effects of WFPBDs on PNP in leprosy, we hope to illuminate data that will lead to the enhanced therapeutic management of this neglected tropical disease.

A review of nutrition in neuropathic pain of leprosy.

Leprosy is a neglected tropical disease (NTD) that continues to burden low- and middle-income countries (LMICs), despite being eliminated as a public health concern by the World Health Organization (WHO) in 2000. The causative agents, Mycobacterium leprae and Mycobacterium lepromatosis, affect nearly 200,000 individuals globally each year, with over 19,000 new cases detected in the Americas in 2020 alone. Canada has experienced an increasing incidence of leprosy, due to rising levels of travel and migration from endemic areas, reaching over 37,000 individuals with leprosy by the end of 2020. Patients experience a spectrum of signs and symptoms including hypopigmented cutaneous macules alongside peripheral neuropathy including peripheral neuropathic pain (PNP) and disabling sensory neuropathies. Despite the development of effective and curative therapeutics via multidrug therapy (MDT), many barriers to treatment adherence and effective immunological control of the pathogen challenge the care of patients with leprosy. Socioeconomic barriers, such as disability-related social stigma and often undiagnosed nutritional deficiencies, have resulted in heightened disease severity. PNP therapeutics are associated with significant side effects and remain ineffective as the majority of individuals will not experience a greater than 30% reduction of symptoms. Nutrient supplementation is known to be instrumental in reducing host oxidative stress, strengthening the immune system and mitigating comorbidities. Likewise, dietary lifestyle interventions known to be physiologically beneficial have recently emerged as powerful tools conferring neuroprotective effects, potentially mitigating PNP severity. However, a significant knowledge gap concerning the effect of adequate nutrition on host immunological control of leprosy and PNP severity exists. Further evaluation of this relationship will provide key insight into the pathogenesis of leprosy, strengthening the current body of literature.

Ofloxacin-Containing Multidrug Therapy in Ambulatory Leprosy Patients: A Case Series.

BACKGROUND: Standard dapsone and clofazimine-containing multidrug therapy (MDT) for leprosy is limited by drug tolerability, which poses treatment adherence barriers. Although ofloxacin-based regimens are promising alternatives, current efficacy and safety data are limited, particularly outside of endemic areas. We evaluated treatment outcomes in patients with leprosy receiving ofloxacin-containing MDT (OMDT) at our center. METHODS: We performed a retrospective chart review of patients treated for leprosy at our center over an 8-year period (2011-2019). Primary outcomes evaluated were clinical cure rate, occurrence of leprosy reactions, antibiotic-related adverse events, and treatment adherence. Analyses were descriptive; however, data were stratified by age, sex, spectrum of disease, region of origin, and treatment regimen, and odds ratios were reported to assess associations with adverse outcomes. RESULTS: Over the enrolment period, 26 patients were treated with OMDT (n = 19 multibacillary, n = 7 paucibacillary), and none were treated with clofazimine-based standard MDT. At the time of analysis, 23 patients (88%) had completed their course of treatment, and all were clinically cured, while 3 (12%) were still on treatment. Eighteen patients (69%) experienced either ENL (n = 7, 27%), type 1 reactions (n = 7, 27%), or both (n = 4, 15%). No patients stopped ofloxacin due to adverse drug effects, and there were no cases of allergic hypersensitivity, tendinopathy or rupture, or C. difficile colitis. CONCLUSIONS: We demonstrate a high cure rate and tolerability of OMDT in this small case series over an 8-year period, suggesting its viability as an alternative to standard clofazimine-containing MDT.

Implementation and evaluation of a quality and safety tool for ambulatory strongyloidiasis patients at high risk of adverse outcome.

BACKGROUND: Strongyloidiasis is a common infection in Canadian migrants that can cause life-threatening hyperinfection in immunosuppressed hosts. We designed and implemented a safety tool to guide management of patients with Strongyloides in order to prevent adverse outcomes. Methods: Patients treated at our centre for strongyloidiasis from January 1, 2013 to December 31, 2015 were identified through our ivermectin access log. Patients were categorized into pre-implementation and post-implementation groups. A retrospective chart review for predefined variables was conducted. RESULTS: Of 37 patients with strongyloidiasis, 26 were in the pre-implementation group and 11 were in the post-implementation group. Documented seroreversion (positive to negative) occurred in 42.1% of patients pre-implementation and 62.5% of patients post-implementation (p = 0.420). Documented stool clearance occurred in 80.0% of patients pre-implementation and 100.0% of patients post-implementation (p = 1.000). More patients were screened for HTLV-1 coinfection post-implementation (80.0%) versus pre-implementation (30.8%) (p = 0.011). Loss to follow-up after treatment occurred in 23.1% of patients pre-implementation and 20.0% of patients post-implementation (p = 1.000). CONCLUSIONS: The safety tool may be useful in the treatment of patients with strongyloidiasis to improve documentation of patient outcomes and standardize care. Future research should include a powered prospective study.

Evaluation of safety tool for ambulatory leprosy patients at risk of adverse outcome.

BACKGROUND: Leprosy is a potentially debilitating disease of the skin and nerves that requires a complex management approach consisting of laboratory monitoring, screening for factors that will adversely affect outcome with corticosteroids, engagement of allied health services, and prolonged follow-up. Given the complexities of leprosy management, a safety tool was developed and implemented in the Tropical Disease Unit at Toronto General Hospital. Our objective was to evaluate the utility of the tool using a retrospective chart review. METHODS: We reviewed the charts of patients with leprosy treated over a 3.5-year period: up to 3 years prior to tool implementation, and 6-months following implementation. Pre-determined outcomes of interest included: loss to follow-up; monitoring of laboratory parameters; allied health services engagement; baseline ophthalmologic assessment; and risk mitigation interventions. RESULTS: Of 17 patients enrolled, 8 were treated pre-implementation, and 9 post-implementation. Five (29.4%) pre-implementation patients were lost to follow-up compared to none post-implementation (p = 0.009). One (12.5%) pre-implementation patient was sent for baseline ophthalmologic assessment versus 8 (88.9%) post-implementation (p = 0.0034). Only post-implementation patients received referrals for occupational therapy and social work, with 77.8% (n = 7) receiving occupational therapy (p = 0.0023) and 33.3% (n = 3) social work (p = 0.2059). Laboratory parameters such as hemoglobin, hepatic transaminases, and methemoglobin were routinely monitored for patients on dapsone irrespective of tool implementation. CONCLUSIONS: Implementation of a leprosy-specific safety tool has established a user-friendly method for systemizing all elements of care, and ensuring the involvement of allied health services necessary for optimizing health outcomes.

Strongyloidiasis in Ontario: Performance of diagnostic tests over a 14-month period.

BACKGROUND: We evaluated the performance of stool microscopy, serology, and real time PCR (qPCR) for the diagnosis of strongyloidiasis at our reference laboratory. METHODS: Using a convenience sample of specimens submitted between April 1, 2014 and May 31, 2015, positivity rates and performance characteristics were calculated. RESULTS: During the enrolment period, 17,933 stool specimens were examined for O&P, 14 of which were positive for Strongyloides larvae. For stool specimens serially positive for larvae, mean duration of larval shedding was 12.7 days following the initial positive specimen, while for sputum and urine, it was 12 and 2 days, respectively. During the enrolment period, 3258 specimens were processed for Strongyloides serology, 200 of which were reactive (6.1%), 210 indeterminate (6.5%), and 2848 non-reactive (87.4%). qPCR was positive in 11 of 12 (91.7%) stool specimens containing larvae, and negative in all stool specimens without larvae by microscopy. There was no cross-reactivity of Strongyloides-specific qPCR to other stool protozoa or helminths. CONCLUSIONS: In the absence of immunosuppression, larval burden in strongyloidiasis is low, limiting the utility of microscopy, and favoring serologic testing. However, false negative serology can occur in those with hyperinfection necessitating a combined diagnostic approach. qPCR was insufficiently sensitive to replace microscopy for detection of larvae.

Evaluation of a programme for 'Rapid Assessment of Febrile Travelers' (RAFT): a clinic-based quality improvement initiative.

BACKGROUND: Fever in the returned traveller is a potential medical emergency warranting prompt attention to exclude life-threatening illnesses. However, prolonged evaluation in the emergency department (ED) may not be required for all patients. As a quality improvement initiative, we implemented an algorithm for rapid assessment of febrile travelers (RAFT) in an ambulatory setting. METHODS: Criteria for RAFT referral include: presentation to the ED, reported fever and travel to the tropics or subtropics within the past year. Exclusion criteria include Plasmodium falciparum malaria, and fulfilment of admission criteria such as unstable vital signs or significant laboratory derangements. We performed a time series analysis preimplementation and postimplementation, with primary outcome of wait time to tropical medicine consultation. Secondary outcomes included number of ED visits averted for repeat malaria testing, and algorithm adherence. RESULTS: From February 2014 to December 2015, 154 patients were seen in the RAFT clinic: 68 men and 86 women. Median age was 36 years (range 16-78 years). Mean time to RAFT clinic assessment was 1.2±0.07 days (range 0-4 days) postimplementation, compared to 5.4±1.8 days (range 0-26 days) prior to implementation (p<0.0001). The RAFT clinic averted 132 repeat malaria screens in the ED over the study period (average 6 per month). Common diagnoses were: traveller's diarrhoea (n=27, 17.5%), dengue (n=12, 8%), viral upper respiratory tract infection (n=11, 7%), chikungunya (n=10, 6.5%), laboratory-confirmed influenza (n=8, 5%) and lobar pneumonia (n=8, 5%). CONCLUSIONS: In addition to provision of more timely care to ambulatory febrile returned travellers, we reduced ED bed-usage by providing an alternate setting for follow-up malaria screening, and treatment of infectious diseases manageable in an outpatient setting, but requiring specific therapy.

Management of imported cutaneous larva migrans: A case series and mini-review.

BACKGROUND: Cutaneous larva migrans (CLM), a zoonotic helminthiasis imported to Canada by travelers to the tropics, causes morbidity due to severe, intractable pruritus. Treatment in Canada is only available through the Special Access Program (SAP) of Health Canada, thus, many patients are prescribed ineffective courses of non-targeted therapy. OBJECTIVE: We analyzed patients with CLM referred to our specialized Tropical Disease Unit (TDU) having failed non-targeted therapy prior to referral, and characterized demographic and travel related correlates of CLM. METHODS: Patients with CLM evaluated between June 2012 and December 2014 were identified through our SAP application log, and charts were reviewed for demographic, clinical, and travel-related data following IRB approval. RESULTS: 25 patients with CLM were identified: 12 women, and 13 men. Median age was 35 years (range 4-58 years). Patients had primarily acquired their CLM in the Caribbean (80%), with Jamaica being the most well represented source destination (N = 10, 40%). Reported symptoms included intense, function-limiting pruritus (N = 25, 100%) and loss of sleep (N = 3, 12%). Twelve patients (48%) with CLM had received at least 1 course of non-targeted therapy prior to referral. Non-targeted therapies included topical steroids (N = 7), cryotherapy (N = 3), oral antibiotics (N = 2), and oral mebendazole (N = 11). Median duration of symptoms was 34 days (range 5-226 days). Of 25 patients with CLM, 23 (92%) were prescribed a single 3-day course of albendazole and responded appropriately, and 2 (8%) required a second 3-day course of albendazole. CONCLUSIONS: Although CLM is non-communicable and of little public health relevance in Canada, it causes significant morbidity. A substantial proportion of patients with CLM referred to our specialized TDU had a prolonged course of illness and were prescribed ineffective and non-targeted therapies. Oral albendazole or ivermectin, or topical thiabendazole, are the drugs of choice for CLM, and should be prescribed as first-line therapy.