Health issues and related health-seeking behaviours of snakebite patients after hospital discharge: A cohort study from rural Sri Lanka.

We aimed to assess the unresolved health issues experienced by a cohort of snakebite survivors and their health-seeking behaviours during the first three months after the snakebite. Patients from the Anuradhapura snakebite cohort admitted to the Teaching Hospital Anuradhapura, Sri Lanka, from July 2021 to June 2022 were recruited. Patients were interviewed over the telephone three weeks and three months post-bite to collect data on unresolved health problems post-discharge, patient's adherence to the review plan, newly experienced health issues, health-seeking behaviours and the effect on daily routine. Only snakebite survivors who could be contacted at both three weeks and three months were included. Of 710 eligible patients, 384 (54%) were contactable at both reviews. On discharge from the hospital, 248/384 (65%) had unresolved effects of the snakebite, including 224/384 (58%) who had local effects. The unresolved health problems were reported by patients bitten by H. hypnale (54%), D. russelii (23%), and unidentified snakes (19%). At three weeks and three months, 98/384 (26%) and 52/384 (14%) still had unresolved local effects of envenoming, respectively. Of 144/384 (38%) who were advised to attend review visits post-discharge, mostly to assess renal function, 118 (82%) complied. 112/384 (29%) patients reported self-motivated treatment seeking for unresolved effects of snakebite over the three months. Of them, 87 (78%) visited Sri Lankan indigenous medical practitioners. Patients missed a median of two working days (IQR: 2-4 days) post-discharge. 26 (6.7%) were unable to return to work at 3 weeks, and five patients at 3 months. In rural Sri Lanka, a significant number of viper bite patients leave hospital with mild persistent local effects, which commonly leads to them seeking further treatment. Despite that, almost all snakebite survivors had returned to work at three months post-bite.

Incidence of serum sickness following Indian polyvalent antivenom therapy in a cohort of snake-envenomed patients in rural Sri Lanka.

INTRODUCTION: Serum sickness is a poorly reported delayed adverse reaction following snake antivenom therapy. We aimed to assess the frequency of serum sickness associated with administering Indian polyvalent antivenom in Sri Lanka. METHODS: We recruited patients from the Anuradhapura snakebite cohort who were admitted to a rural tertiary care hospital in Sri Lanka over one year period. Patients were interviewed over the phone 21 to 28 days post-envenoming to collect data on clinical effects: fever/chills, arthralgia/myalgia, rash, malaise, headache, abdominal pain, and nausea/vomiting. The presence of three or more symptoms between the 5th to 20th days after snake envenoming was defined as serum sickness. RESULTS: We were able to contact 98/122 (80%) patients who received antivenom and 423/588 (72%) who did not receive antivenom during the study period. The treated patients received a median dose of 20 vials (interquartile range: 20-30) of Indian polyvalent antivenom and of them, 92 (92%) received premedication. However, 67/98 (68%) developed acute adverse reactions to antivenom, including 19/98 (19%) developing anaphylaxis. Only 4/98 (4%) who received antivenom met the criteria for serum sickness, compared to none who did not receive antivenom therapy. All patients who developed serum sickness were envenomed by Russell's vipers, were premedicated, and received VINS Bioproducts antivenom. Three of them were treated with hydrocortisone in the acute stage, as premedication or as a treatment for acute adverse reactions of antivenom. Although all four patients sought medical advice for their symptoms, only one was clinically suspected to be serum sickness and treated, while the others were treated for infections. CONCLUSIONS: We confirmed that Indian polyvalent antivenom use in Sri Lanka is associated with high rates of acute adverse reactions. In contrast to studies of other antivenoms only a small proportion of patients developed serum sickness.

Does snake envenoming cause chronic kidney disease? A cohort study in rural Sri Lanka.

BACKGROUND: There is limited information on the risk of chronic kidney disease (CKD) following snakebite and its relationship with chronic interstitial nephritis in agricultural communities (CINAC). We aimed to investigate CKD in patients with a confirmed snakebite in rural Sri Lanka. METHODS: Patients prospectively recruited to the Anuradhapura snakebite cohort with authenticated bites were followed up. Two groups of patients were followed up: 199 patients in group I with a snakebite (August 2013-October 2014), reviewed after 4 years, and 168 patients in group II with a snakebite (May 2017-August 2018), reviewed after one year, with serum creatinine (estimated glomerular filtration rate [eGFR]) and urinary albumin to creatinine ratio (ACR). RESULTS: There were 12/199 (6%) in group I and 9/168 (5%) in group II with AKI following snakebite; 3/12 in group I and 2/9 in group II had haemodialysis. On review after 1 and 4 years, no patient had CKD and all had an eGFR ≥60 mL/min/1.73m2. Of 234 patients with a creatinine measured on discharge, 17/140 in group I and 11/94 in group II had a low eGFR (<60mL/min/1.73m2). In group I, 14/17 had a normal eGFR after four years, including 11/12 who had AKI following snakebite, and the 3/17 with a low eGFR on review had CKD or co-morbidities for CKD. In group II, 10/11 had a normal eGFR after one year, including all nine patients with AKI following snakebite, and the one patient with a low eGFR on review had CKD. Fifty patients (25%) in group I and 43 (26%) in group II had a high urinary ACR on review, all but two in each group had microalbuminuria. Multivariate logistic regression showed in group I that only comorbidities for CKD were associated with high urinary ACR, and in group II comorbidities for CKD, snakebite associated AKI and snake type were associated with high urinary ACR. All nine patients from both groups with a low eGFR (CKD stages 3-5) had CKD prior to the snakebite or treatment for hypertension or diabetes. CONCLUSION: There was no significant association between snakebite-associated AKI and CKD in patients followed up from a snakebite cohort post-bite. Microalbuminuria was common in these patients but likely associated with hypertension, diabetes mellitus and CINAC in this rural farming population.

Long-term health effects perceived by snakebite patients in rural Sri Lanka: A cohort study.

The acute effects of snakebite are often emphasized, with less information on long-term effects. We aimed to describe the long-term health effects perceived by patients followed up after confirmed snakebites. Two groups of snakebite patients (>18y) from the Anuradhapura snakebite cohort were reviewed: Group I had a snakebite during August 2013-October 2014 and was reviewed after 4 years, and group II had a snakebite during May 2017-August 2018, and was reviewed after one year. Patients were invited by telephone, by sending letters, or doing home visits, including 199 of 736 patients (27%) discharged alive from group I and 168 of 438 patients (38%) from group II, a total of 367 followed up. Health effects were categorised as musculoskeletal, impact on daily life, and medically unexplained. Health issues were attributed to snakebite in 107/199 patients (54%) from group I and 55/168 patients (33%) from group II, suggesting the proportion with health issues increases with time. Sixteen patients (all viperine bites) had permanent musculoskeletal problems, none with a significant functional disability affecting daily routine. 217/367 reported being more vigilant about snakes while working outdoors, but only 21/367 were using protective footwear at review. Of 275 farmers reviewed, only six (2%) had restricted farming activities due to fear of snakebite, and only one stopped farming. 104/199 (52%) of group I and 42/168 (25%) of group II attributed non-specific symptoms (fatigue, body aches, pain, visual impairment) and/or oral cavity-related symptoms (avulsed teeth, loose teeth, receding gums) to the snakebite, which cannot be explained medically. In multivariate logistic regression, farming, type of snake, antivenom administration, and time since snakebite were associated with medically unexplained symptoms. The latter suggests medically unexplained effects increased with time. Based on two groups of snakebite patients reviewed one and four years post-bite, we show that long-term musculoskeletal disabilities are uncommon and not severe in snakebite survivors in rural Sri Lanka. However, a large portion of patients complain of various non-specific general and oral symptoms, not explainable based on the known pathophysiology of snakebite. These perceived effects of snakebite were more common in patients with systemic envenoming, and were more frequent the longer the time post-bite.

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.

Long-term Effects of Snake Envenoming.

Long-term effects of envenoming compromise the quality of life of the survivors of snakebite. We searched MEDLINE (from 1946) and EMBASE (from 1947) until October 2018 for clinical literature on the long-term effects of snake envenoming using different combinations of search terms. We classified conditions that last or appear more than six weeks following envenoming as long term or delayed effects of envenoming. Of 257 records identified, 51 articles describe the long-term effects of snake envenoming and were reviewed. Disability due to amputations, deformities, contracture formation, and chronic ulceration, rarely with malignant change, have resulted from local necrosis due to bites mainly from African and Asian cobras, and Central and South American Pit-vipers. Progression of acute kidney injury into chronic renal failure in Russell's viper bites has been reported in several studies from India and Sri Lanka. Neuromuscular toxicity does not appear to result in long-term effects. Endocrine anomalies such as delayed manifestation of hypopituitarism following Russell's viper bites have been reported. Delayed psychological effects such as depressive symptoms, post-traumatic stress disorder and somatisation have been reported. Blindness due to primary and secondary effects of venom is a serious, debilitating effect. In general, the available studies have linked a clinical effect to a snakebite in retrospect, hence lacked accurate snake authentication, details of acute management and baseline data and are unable to provide a detailed picture of clinical epidemiology of the long-term effects of envenoming. In the future, it will be important to follow cohorts of snakebite patients for a longer period of time to understand the true prevalence, severity, clinical progression and risk factors of long-term effects of snake envenoming.