A prospective observational phase IV study on effectiveness of animal derived polyclonal antibody antivenoms against West African carpet viper (Echis romani) induced coagulopathy and mortality.

Conventional polyclonal antibody antivenoms are the mainstay of snakebite therapy. They have not been proven to be efficacious in randomized placebo controlled clinical trials among severely envenomed patients. There is also paucity of evidence on effectiveness especially in routine use. The current study evaluated their effectiveness in post marketing use among those managed with and without antivenom as regards to reversal of venom induced coagulopathy defined using the 20 min Whole Blood Clotting Test [20WBCT] and in averting death. The effectiveness of antivenom was evaluated among 5467 patients predominantly envenomed by the West African carpet viper (Echis romani) at 3 hospitals in Nigeria from 2021 to 2022. Two antivenoms Echitab G (EG) and Echitab ICP Plus (EP) were able to restore normal clotting within 6 h of administration in 58.0% [95% Confidence Interval (95%CI)] (51.2-64.5%) and 91.7% (90.4-93.0%) of patients respectively. They were able to restore normal clotting within 24 h of administration in 96.9% (94.0-98.7%) and 99.0% (98.4-99.4%) of patients respectively. The Odds Ratio [OR (95%CI)] of dying among patients with positive 20WBCT who were treated with ≥1 vial of either EG or EP compared to those not treated was 0.06 (0.02-0.23) and 0.07 (0.03-0.15) respectively. This equated to antivenom protection against in-hospital mortality of 93-94% among patients with confirmed coagulopathy though the benefit appeared abrogated among those without coagulopathy. The untreated natural mortality was 15.94% (95%CI:8.24-26.74%) without antivenom therapy while the overall mortality was 84/5105 (1.65%; 95%CI:1.32-2.03%. The Number Needed to Treat (NNT) to avert a death was 7 patients among those with coagulopathy. Antivenoms were safe with mild early adverse reactions observed among 2.6% (95%CI:2.13-3.08%) of antivenom recipients. Polyclonal antibody antivenoms are effective and safe for treating coagulopathic envenomed patients in Nigeria.

Diagnostic characteristics of the 20-minute whole blood clotting test in detecting venom-induced consumptive coagulopathy following carpet viper envenoming.

INTRODUCTION: Envenoming by Echis spp. (carpet or saw-scaled vipers) causes haemorrhage and coagulopathy and represents a significant proportion of snakebites in the savannah regions of West Africa. Early diagnosis of envenoming is crucial in the management of these patients and there is limited evidence on the utility of the 20-minute whole blood clotting test (20WBCT) in diagnosing venom-induced consumptive coagulopathy (VICC) following envenoming by Echis ocellatus. METHODS: A prospective observational cohort study was conducted at the Kaltungo General Hospital in North-eastern Nigeria from September 2019 to September 2021. Standardised 20WBCTs were conducted by trained hospital staff and citrated plasma samples were collected at numerous timepoints. Prothrombin time (PT) and international normalised ratio (INR) were determined using a semi-automated analyser and INR values were calculated using international sensitivity indices (ISI). The sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and likelihood ratios of the 20WBCT compared to an INR ≥ 1.4 were calculated, alongside 95% confidence intervals. RESULTS: We enrolled 121 patients into our study, with a median age of 26 (18.0-35.0) years and a male predominance (75.2%). The 20WBCT was positive (abnormal) in 101 out of 121 patients at timepoint 0h, of which 95 had an INR ≥ 1.4, giving a sensitivity of 87.2% (95%CI 79.4-92.8). Among patients with a negative 20WBCT (normal), six had an INR < 1.4 giving a specificity of 50% (95%CI 21.1-78.9). The positive and negative likelihood ratios were 1.7 (95%CI 1.6-1.9) and 0.3 (95%CI 0.1-0.4) respectively. CONCLUSION: The 20WBCT is a simple, cheap, and easily accessible bedside test with a high sensitivity for the detection of patients with venom induced consumptive coagulopathy (VICC) following envenoming by E. ocellatus, although false positives do occur. Repeated 20WBCTs can identify patients with new, persistent, and rebound coagulopathy.

Comparison of snakebite in children and adults in Nigeria.

Snakebite envenoming is a major global public health problem and disproportionately affects children. To study the differences in clinical presentation and outcomes between children and adults, 2922 snakebite patients of whom 30.3% were children were analysed. Most bites (>75%) were in the lower. Features of local envenoming were commoner among children compared to adults (p < 0.05), while systemic envenoming features, mortality and complications were similar, p = 0.356, p = 0.12, and p = 0.16 respectively.

Performance of the 20 minutes Whole Blood Clotting Test in detection, monitoring and antivenom therapy of West African Carpet viper (Echis romani) envenoming in resource constrained settings in Nigeria.

The 20 minutes Whole Blood Clotting Test (20WBCT) was evaluated in 1541 snakebite patients at 3 hospitals in Nigeria. It was useful in detection, monitoring, guiding antivenom therapy and prognostication of coagulopathy, with initial sensitivity of 84.7% (95%CI:82.7-86.5%) and specificity of 64.3% (95%CI:50.4-76.7%) compared to clinical envenoming. It led to correct decisions regarding administration or withholding antivenom in 97.93% of patients. The proportion of carpet viper (Echis romani) envenomed patients who restored clotting rose steadily following effective antivenom therapy. Patients with positive 20WBCT had severer envenoming, required more blood transfusion, had longer hospital stay and derived higher antivenom protection against death from carpet viper. However, there was no association between positive 20WBCT and fatality or complications.

Livestock herding and Fulani ethnicity are a combined risk factor for development of early adverse reactions to antivenom treatment: Findings from a cross-sectional study in Nigeria.

BACKGROUND: Adverse reactions to antivenom considerably complicate the clinical management of snakebite envenomed patients because it necessitates a temporary suspension of life-saving antivenom, increases costs and can compromise patient outcomes. This study sought to explore the association between cattle-herding occupation and ethnic group and the occurrence of early adverse reactions to antivenom. METHODS: This cross-sectional study was conducted between the 25th April and 11th July 2011 at the Kaltungo General Hospital in north east Nigeria. The exposure variable of cattle-herding occupation showed a strong correlation with the ethnic group variable, thus these were combined into a new variable with three categories (Fulani and herder, either Fulani or herder, and neither Fulani nor herder). The outcome variable was the occurrence of early adverse reactions, defined as any new symptoms occurring within 6 hours of antivenom administration. Odds Ratios were estimated using multivariable logistic regression models controlling for potential confounders. RESULTS: Among 231 envenomed snakebite victims, the overall incidence of early adverse reactions was 11.9% (95% confidence intervals: 8.0-16.9%). Patients who were Fulani and herders had a higher incidence of early adverse reactions compared to patients who were neither Fulani nor herders (20% vs 5.7%). After adjusting for age and gender, victims who were Fulani and herders were 5.9 times more likely to have an early adverse reaction, compared to victims who were neither Fulani nor herders (95% CI: 1.88-18.59; p = 0.002). INTERPRETATION: To the best of our knowledge, this is the first study to provide evidence of higher odds of early adverse reactions among patients from a particular occupation and/or ethnic group. We recommend that snake envenomed patients of Fulani origin be especially closely monitored for adverse reactions, that hospitals receiving these patients be appropriately resourced to manage both envenoming and adverse reactions and that premedication with adrenaline should be considered. Our findings provide an argument for speculation on the influence of immunological or lifestyle-related differences on the occurrence of early adverse reactions to antivenom.

Posttraumatic stress disorder and psycho-social impairment following snakebite in Northeastern Nigeria.

BACKGROUND: Snakebite is a major public health problem among impoverished rural populations causing considerable morbidity and mortality in West Africa. Despite the huge burden of snakebite in this region, psycho-social impairment following snakebite has not been evaluated. In this study, we assessed for features of posttraumatic stress disorder and psycho-social impairment among rural snakebite victims in Northeastern Nigeria. METHODS: Individuals with previous snakebite managed in our facility, defined as exposed to snakebite, and their matched relatives not exposed to snakebite were invited to participate in the study following community mobilization. A retrospective cohort study was conducted evaluating the presence of psycho-social functioning, posttraumatic stress disorder, quality of life, social disability, cognitive impairment, and psychological morbidity using standard tools administered by the investigators, trained nurses, and community health workers. RESULTS: The prevalence of features of posttraumatic stress disorder among those exposed to snakebite compared to those not exposed to snakebite was 43% and 28%, respectively (risk ratio = 1.53; 95% confidence interval: 1.04-2.24; p = 0.024). Subjects exposed to snakebite had significantly poorer quality of life score in the psychological and social domains (p < 0.05). Other psycho-social complications associated with snakebite were impaired family/school functioning and psychological morbidity. No difference in cognitive functioning was observed between the two groups. CONCLUSIONS: Snakebite is complicated by features of posttraumatic stress disorder, poor quality of life, and psycho-social impairments in northeastern Nigeria. Detection, monitoring, and appropriate management interventions should be provided and made more accessible to snakebite victims to ameliorate mental and psychological impairment.

Randomised controlled double-blind non-inferiority trial of two antivenoms for saw-scaled or carpet viper (Echis ocellatus) envenoming in Nigeria.

BACKGROUND: In West Africa, envenoming by saw-scaled or carpet vipers (Echis ocellatus) causes great morbidity and mortality, but there is a crisis in supply of effective and affordable antivenom (ISRCTN01257358). METHODS: In a randomised, double-blind, controlled, non-inferiority trial, "EchiTAb Plus-ICP" (ET-Plus) equine antivenom made by Instituto Clodomiro Picado was compared to "EchiTAb G" (ET-G) ovine antivenom made by MicroPharm, which is the standard of care in Nigeria and was developed from the original EchiTAb-Fab introduced in 1998. Both are caprylic acid purified whole IgG antivenoms. ET-G is monospecific for Echis ocellatus antivenom (initial dose 1 vial) and ET-Plus is polyspecific for E. ocellatus, Naja nigricollis and Bitis arietans (initial dose 3 vials). Both had been screened by pre-clinical and preliminary clinical dose-finding and safety studies. Patients who presented with incoagulable blood, indicative of systemic envenoming by E. ocellatus, were recruited in Kaltungo, north-eastern Nigeria. Those eligible and consenting were randomly allocated with equal probability to receive ET-Plus or ET-G. The primary outcome was permanent restoration of blood coagulability 6 hours after the start of treatment, assessed by a simple whole blood clotting test repeated 6, 12, 18, 24 and 48 hr after treatment. Secondary (safety) outcomes were the incidences of anaphylactic, pyrogenic and late serum sickness-type antivenom reactions. FINDINGS: Initial doses permanently restored blood coagulability at 6 hours in 161/194 (83.0%) of ET-Plus and 156/206 (75.7%) of ET-G treated patients (Relative Risk [RR] 1.10 one-sided 95% CI lower limit 1.01; P = 0.05). ET-Plus caused early reactions on more occasions than did ET-G [50/194 (25.8%) and 39/206 (18.9%) respectively RR (1.36 one-sided 95% CI 1.86 upper limit; P = 0.06). These reactions were classified as severe in 21 (10.8%) and 11 (5.3%) of patients, respectively. CONCLUSION: At these doses, ET-Plus was slightly more effective but ET-G was slightly safer. Both are recommended for treating E. ocellatus envenoming in Nigeria. TRIAL REGISTRATION: Current Controlled Trials ISRCTN01257358.