Approach to Study the Efficacy and Safety of New Complementary and Alternative Medicine Formulations: Lesson during COVID-19 from Sri Lanka.

COVID-19 affected Sri Lanka from early 2020, a time of considerable ignorance accompanied by wide media coverage of a devastating epidemic in Italy and Europe. Many were attracted to complementary and alternative medicine (CAM) or traditional medicine (TM) in this desperate situation. Several preparations were claimed to be effective against COVID-19 globally. Dammika Bandara Syrup© was one such preparation promoted for preventing and treating SARS-CoV-2 infection. It was based on bees' honey, pericarp and mace of Myristica fragrans (nutmeg), the seed of Foeniculum vulgare and fresh rhizome of Zingiber officinale, all believed to have anti-viral properties. Following an unpublished clinical study claiming efficacy, Dammika Bandara Syrup© gained wide media publicity and political patronage. The producer claimed of Goddess Kali revealing the formula added an anthropological, cultural, and religious complexity to the issue. The demand for the product increased rapidly as a debate raged both in public and in the parliament on utilizing such products in combating COVID-19. The Department of Ayurveda, which is statutorily responsible for regulating CAM/TM had to respond to the situation. The legislation to regulate such indigenous medicinal products was weak, and the crisis deepened as thousands converged to the production facility, defying mobility restrictions introduced to control COVID-19. This led to the Ministry of Health requesting academics to form a team and conduct a clinical trial to prove its efficacy. This paper outlines the process and issues faced during the regulatory approval for the trial in a polarized political environment. Some health professionals accused the researchers of bowing to political pressure and questioned the scientific justification for the trial. However, the team considered this as an opportunity to streamline a path for research into CAM/TM therapies in situations such as COVID-19. Several processes were identified and addressed, such as the provisional registration of CAM preparations, assessing the potential efficacy of a CAM product, confirmation of authenticity and safety, standardization and supervision of production respecting cultural identities, obtaining approval for human use, choice of comparators, and ethical issues. We believe the study has helped set standards and a benchmark for CAM and TM research in Sri Lanka.

Demographic, exposure, clinical, biochemical and diagnostic data of febrile patients recruited for the largest field study on leptospirosis in Sri Lanka.

This dataset includes data from febrile patients recruited for a large hospital-based study in Sri Lanka from 2016 to 2019. The variables include primary socio-demographic data, exposure data, clinical data, biochemical and investigation data. Some of these data are available as serial data from admission to discharge daily. Microscopic agglutination test, quantitative PCR of whole blood, urine and serum and culture isolation was performed to diagnose the patients with leptospirosis.

Value-Added Roles of Medical Students During the COVID-19 Pandemic: Assessment of Medical Students' Perceptions and Willingness in Sri Lanka.

PURPOSE: Since the coronavirus disease 2019 (COVID-19) pandemic is an opportune time to introduce the value-added roles of medical students, this study assessed medical students' perceptions and willingness to assist in COVID-19 health sector preparedness and response via value-added roles in Sri Lanka. METHODS: A cross-sectional online survey was conducted among all medical students studying in six batches of the Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, in June 2020. A Google form in English with 10 statements about individual perceptions of medical students' roles and their willingness to assist in the COVID-19 health sector response via value-added roles was used to collect data. The responses were recorded on a five-point Likert scale. The chi-squared test for independence was used to explore the associations between the academic year and the responses to each statement. RESULTS: Out of 856 (response rate 79.6%) study participants, the majority were females (n=601, 70.2%). The majority (n=804, 93.9%) reported that they have a responsibility to contribute to the country's COVID-19 health sector response. There was a statistically significant association between medical students' perceived level of clinical knowledge, having the clinical skills to assist in the COVID-19 health sector response and academic year (p<0.001). The commonly identified value-added roles were developing (n=770, 89.9%) and disseminating (n=744, 86.9%) health education messages, and field contact tracing activities (n=653, 76.3%). Other value-added roles were assisting the curative health sector in COVID-19 patient management (n=380, 44.4%) and other non-COVID-19 patient management (n=463, 54.1%). CONCLUSION: Medical students are mostly willing to engage in preventive health sector value-added roles and, to a lesser extent, in curative health sector value-added roles during the COVID-19 outbreak. However, medical educators need to clearly define the value-added roles and provide adequate training and supervision for medical students across academic years to enable them to combine learning with making meaningful contributions to the health-care system during the COVID-19 pandemic.

Time delays in treatment of snakebite patients in rural Sri Lanka and the need for rapid diagnostic tests.

Delays in treatment seeking and antivenom administration remain problematic for snake envenoming. We aimed to describe the treatment seeking pattern and delays in admission to hospital and administration of antivenom in a cohort of authenticated snakebite patients. Adults (> 16 years), who presented with a confirmed snakebite from August 2013 to October 2014 were recruited from Anuradhapura Hospital. Demographic data, information on the circumstances of the bite, first aid, health-seeking behaviour, hospital admission, clinical features, outcomes and antivenom treatment were documented prospectively. There were 742 snakebite patients [median age: 40 years (IQR:27-51; males: 476 (64%)]. One hundred and five (14%) patients intentionally delayed treatment by a median of 45min (IQR:20-120min). Antivenom was administered a median of 230min (IQR:180-360min) post-bite, which didn't differ between directly admitted and transferred patients; 21 (8%) receiving antivenom within 2h and 141 (55%) within 4h of the bite. However, transferred patients received antivenom sooner after admission to Anuradhapura hospital than those directly admitted (60min [IQR:30-120min] versus 120min [IQR:52-265min; p<0.0001]). A significantly greater proportion of transferred patients had features of systemic envenoming on admission compared to those directly admitted (166/212 [78%] versus 5/43 [12%]; p<0.0001), and had positive clotting tests on admission (123/212 [58%] versus 10/43 [23%]; p<0.0001). Sri Lankan snakebite patients present early to hospital, but there remains a delay until antivenom administration. This delay reflects a delay in the appearance of observable or measurable features of envenoming and a lack of reliable early diagnostic tests. Improved early antivenom treatment will require reliable, rapid diagnostics for systemic envenoming.

The relationship between the exposure to healthcare settings and colonization with methicillin-resistant Staphylococcus aureus among medical students.

INTRODUCTION: Medical students who engage in clinical learning in healthcare settings can be potential methicillin-resistant Staphylococcus aureus (MRSA) carriers. METHODS: This is a descriptive cross-sectional study having a follow-up approach. Three batches of medical students who were studying at the Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka (1st, 3rd and 5th study years of MBBS course) were screened for nasal and axillary MRSA colonization. The first-year students were screened before and 6 months after clinical learning. The knowledge of the students about infection control was scored (percentage) using a questionnaire in the one week before and later one year after the hospital exposure. Data was compared using two-sample t test. RESULTS: The percentage of MRSA colonization was 6.36% (7/110) and 49.57% (59/119) before clinical exposure and after 2.5 years of exposure, respectively (p<0.012). The percentage of correct responses obtained by the students for the questionnaire about infection control was 28% and 66.9% one week before the exposure to the hospitals and one year after the exposure to the hospitals, consecutively. CONCLUSIONS: MRSA carriage was significantly associated with the time duration of the clinical training of the medical students. The knowledge of students about infection control was significantly inadequate one week before the hospital exposure and they have gained the knowledge only after being exposed to the hospitals.

Hyponatraemia and seizures in Merrem's hump-nosed pit viper (Hypnale hypnale) envenoming: a case report.

BACKGROUND: Hump-nosed pit vipers (Genus: Hypnale) are medically important snakes in Sri Lanka and South India. Merrem's Hump-nosed pit viper (Hypnale hypnale) frequently leads to potentially fatal envenomings in Sri Lanka and India. Venom-induced consumption coagulopathay (VICC), local envenoming and acute kidney injury (AKI) are the commonest effects of the envenoming by this snake. CASE PRESENTATION: We report a previously unreported presentation of H. hypnale envenoming, with an isolated urinary salt loss leading to moderate hyponatraemia resulting seizures. The patient was treated with careful fluid and electrolyte management. No antivenom is currently available for H. hypnale envenoming. CONCLUSION: In the absence of any evidence of venom induced consumptive coagulopathy, acute kidney injury and cerebral haemorrhage, we hypothesize that this effect is likely due to the presence of a natriuretic peptide in H. hypnale venom, similar to the natriuretic peptides identified in few other snake venoms.

Regulation of herbal medicine use based on speculation? A case from Sri Lanka.

Chronic Kidney Disease of Unknown aetiology is a significant public health problem in Sri Lanka. The final report by the WHO mission recommended regulation of herbal medicines containing aristolochic acid, which is an established nephrotoxin. The use of Complimentary and Alternative Medicine (CAM) has a history of more than 2500 years in Sri Lanka. Aristolochia species are rarely used in Ayurveda and traditional medicine in Sri Lanka. Before regulating the analysis of herbal preparations using Aristolochia, collecting data from CAM practitioners regarding the use of Aristolochia is necessary. Analysis of Ayurveda pharmacopeia shows the doses used are negligible and some preparations are used for external applications.

Exertional heat stroke in a young military trainee: is it preventable?

BACKGROUND: Heat stroke is a life-threatening condition with exertional heat stroke occurring frequently among soldiers and athletes. Because of its common occurrence, many military trainees practice preventive measures prior to any activity requiring severe exertion. Although it is said to be common in practice, different presentations of heat stroke are scarcely described in literature. CASE PRESENTATION: We describe a case of an exertional heat stroke in a 23-year-old male Sinhalese soldier who developed early changes of renal failure, liver failure and rhabdomyolysis. The patient initially presented with convulsions, delirium and loss of consciousness to an outside health care facility before being transferred to our institution. CONCLUSION: It is clear that heat stroke does occur in military trainees while preventive strategies are being practiced. It is important for those who provide healthcare to soldiers to provide proper advice on how to identify impending heat stroke prior to any exercises resulting in severe physical exertion. Further, treating physicians should educate all military trainees about preventive strategies.

Neurotoxicity in Russell's viper (Daboia russelii) envenoming in Sri Lanka: a clinical and neurophysiological study.

CONTEXT: Russell's viper is more medically important than any other Asian snake, due to number of envenoming's and fatalities. Russell's viper populations in South India and Sri Lanka (Daboia russelii) cause unique neuromuscular paralysis not seen in other Russell's vipers. OBJECTIVE: To investigate the time course and severity of neuromuscular dysfunction in definite Russell's viper bites, including antivenom response. METHODOLOGY: We prospectively enrolled all patients (>16 years) presenting with Russell's viper bites over 14 months. Cases were confirmed by snake identification and/or enzyme immunoassay. All patients had serial neurological examinations and in some, single fibre electromyography (sfEMG) of the orbicularis oculi was performed. RESULTS: 245 definite Russell's viper bite patients (median age: 41 years; 171 males) presented a median 2.5 h (interquartile range: 1.75-4.0 h) post-bite. All but one had local envenoming and 199 (78%) had systemic envenoming: coagulopathy in 166 (68%), neurotoxicity in 130 (53%), and oliguria in 19 (8%). Neurotoxicity was characterised by ptosis (100%), blurred vision (93%), and ophthalmoplegia (90%) with weak extraocular movements, strabismus, and diplopia. Neurotoxicity developed within 8 h post-bite in all patients. No bulbar, respiratory or limb muscle weakness occurred. Neurotoxicity was associated with bites by larger snakes (p < 0.0001) and higher peak serum venom concentrations (p = 0.0025). Antivenom immediately decreased unbound venom in blood. Of 52 patients without neurotoxicity when they received antivenom, 31 developed neurotoxicity. sfEMG in 27 patients with neurotoxicity and 23 without had slightly elevated median jitter on day 1 compared to 29 normal subjects but normalised thereafter. Neurological features resolved in 80% of patients by day 3 with ptosis and weak eye movements resolving last. No clinical or neurophysiological abnormality was detected at 6 weeks or 6 months. CONCLUSION: Sri Lankan Russell's viper envenoming causes mild neuromuscular dysfunction with no long-term effects. Indian polyvalent antivenom effectively binds free venom in blood but does not reverse neurotoxicity.

Neuromuscular Effects of Common Krait (Bungarus caeruleus) Envenoming in Sri Lanka.

OBJECTIVE: We aimed to investigate neurophysiological and clinical effects of common krait envenoming, including the time course and treatment response. METHODOLOGY: Patients with definite common krait (Bungarus caeruleus) bites were recruited from a Sri Lankan hospital. All patients had serial neurological examinations and stimulated concentric needle single-fibre electromyography (sfEMG) of orbicularis oculi in hospital at 6 wk and 6-9 mth post-bite. PRINCIPAL FINDINGS: There were 33 patients enrolled (median age 35 y; 24 males). Eight did not develop neurotoxicity and had normal sfEMG. Eight had mild neurotoxicity with ptosis, normal sfEMG; six received antivenom and all recovered within 20-32 h. Seventeen patients developed severe neurotoxicity with rapidly descending paralysis, from ptosis to complete ophthalmoplegia, facial, bulbar and neck weakness. All 17 received Indian polyvalent antivenom a median 3.5 h post-bite (2.8-7.2 h), which cleared unbound venom from blood. Despite this, the paralysis worsened requiring intubation and ventilation within 7 h post-bite. sfEMG showed markedly increased jitter and neuromuscular blocks within 12 h. sfEMG abnormalities gradually improved over 24 h, corresponding with clinical recovery. Muscle recovery occurred in ascending order. Myotoxicity was not evident, clinically or biochemically, in any of the patients. Patients were extubated a median 96 h post-bite (54-216 h). On discharge, median 8 days (4-12 days) post-bite, patients were clinically normal but had mild sfEMG abnormalities which persisted at 6 wk post-bite. There were no clinical or neurophysiological abnormalities at 6-9 mth. CONCLUSIONS: Common krait envenoming causes rapid onset severe neuromuscular paralysis which takes days to recover clinically consistent with sfEMG. Subclinical neuromuscular dysfunction lasts weeks but was not permanent. Antivenom effectively cleared venom but did not prevent worsening or reverse neuromuscular paralysis.

Viper bites complicate chronic agrochemical nephropathy in rural Sri Lanka.

Snakebite is a common occupational health hazard among Sri Lankan agricultural workers, particularly in the North Central Province. Viperine snakes, mainly Russell's viper envenomation, frequently lead to acute renal failure. During the last two decades, an agrochemical nephropathy, a chronic tubulointerstitial disease has rapidly spread over this area leading to high morbidity and mortality. Most of the epidemiological characteristics of these two conditions overlap, increasing the chances of co-occurrence. Herein, we describe four representative cases of viperine snakebites leading to variable clinical presentations, in patients with chronic agrochemical nephropathy, including two patients presented with acute and delayed anuria. These cases suggest the possibility of unusual manifestations of snakebite in patients with Sri Lankan agrochemical nephropathy, of which the clinicians should be aware. It could be postulated that the existing scenario in the Central America could also lead to similar clinical presentations.

Viper bites complicate chronic agrochemical nephropathy in rural Sri Lanka

Snakebite is a common occupational health hazard among Sri Lankan agricultural workers, particularly in the North Central Province. Viperine snakes, mainly Russell’s viper envenomation, frequently lead to acute renal failure. During the last two decades, an agrochemical nephropathy, a chronic tubulointerstitial disease has rapidly spread over this area leading to high morbidity and mortality. Most of the epidemiological characteristics of these two conditions overlap, increasing the chances of co-occurrence. Herein, we describe four representative cases of viperine snakebites leading to variable clinical presentations, in patients with chronic agrochemical nephropathy, including two patients presented with acute and delayed anuria. These cases suggest the possibility of unusual manifestations of snakebite in patients with Sri Lankan agrochemical nephropathy, of which the clinicians should be aware. It could be postulated that the existing scenario in the Central America could also lead to similar clinical presentations.

Viper bites complicate chronic agrochemical nephropathy in rural Sri Lanka

Snakebite is a common occupational health hazard among Sri Lankan agricultural workers, particularly in the North Central Province. Viperine snakes, mainly Russell’s viper envenomation, frequently lead to acute renal failure. During the last two decades, an agrochemical nephropathy, a chronic tubulointerstitial disease has rapidly spread over this area leading to high morbidity and mortality. Most of the epidemiological characteristics of these two conditions overlap, increasing the chances of co-occurrence. Herein, we describe four representative cases of viperine snakebites leading to variable clinical presentations, in patients with chronic agrochemical nephropathy, including two patients presented with acute and delayed anuria. These cases suggest the possibility of unusual manifestations of snakebite in patients with Sri Lankan agrochemical nephropathy, of which the clinicians should be aware. It could be postulated that the existing scenario in the Central America could also lead to similar clinical presentations.

First authenticated case of Sri Lankan flying snake (Chrysopelea taprobanica) bite.

Flying snakes (Genus Chrysopelea) are a group of ophisthoglyphous colubrids in South and South East Asia known for gliding in the air. Of the five species of flying snakes, Sri Lankan flying snake, Chrysopelea taprobanica, is endemic to Sri Lanka. Authenticated bites and the venom characteristics of this uncommon snake remain unknown. We report the first authenticated case of C taprobanica bite, in which a 45-year-old woman had signs of mild local envenoming after the bite, with no evidence of systemic envenoming.

Acute myocardial infarction following a possible direct intravenous bite of Russell's viper (Daboia russelli).

BACKGROUND: Russell's viper (Daboia russelli) bites lead to high morbidity and mortality in South Asia. Although variety of clinical manifestations is reported in viper bite victims, myocardial ischemic events are rare. CASE PRESENTATION: We report a unique case of inferior wall ST elevation myocardial infarction due to a Russell's viper bite over a vein with possible direct intravenous envenoming, in a young male with no past history or family history suggestive of ischemic cardiac disease, from Sri Lanka. In addition, the possible mechanisms of myocardial ischemia in snake bite victims are also briefly discussed. CONCLUSION: Importance of the awareness of physicians on the rare, yet fatal manifestations of snake envenoming is highlighted.