The identity of the Sri Lankan Amblypharyngodon (Teleostei, Cyprinidae)

Morphological and molecular analyses of specimens representative of the geographic range of the cyprinid genus Amblypharyngodon in Sri Lanka suggest the presence of only a single species in the island, for which the name Amblypharyngodon grandisquamis Jordan & Starks, 1917, is available. Amblypharyngodon grandisquamis is a species endemic to Sri Lanka, distributed across the lowlands of both of the island’s main climatic zones. It is distinguished from all other species of Amblypharyngodon, including the three species recorded from peninsular India (A. mola, A. microlepis, and A. melettinus), by a suite of characters that includes a body depth of 26.9–31.2% of the standard length (SL), 42–56 scales in the lateral series (of which usually 8–16 are pored), 20–24 circumpeduncular scales, 14–17 scale rows between the origins of the dorsal and pelvic fins, a dorsal-fin height of 21.1–27.6% SL, 18–19 caudal vertebrae and an eye diameter of 22.7–30.5% of the head length. Amblypharyngodon grandisquamis differs from A. melettinus and A. mola by uncorrected pairwise genetic distances of more than 9% and 6%, respectively, for the mitochondrial cytochrome oxidase subunit 1 (COI) gene

Erratum to: The in vitro toxicity of venoms from South Asian Hump-nosed pit vipers (Viperidae: Hypnale)

Hump-nosed pit vipers (Genus Hypnale) are venomous snakes from South India and Sri Lanka. Envenoming by Hypnale species may cause significant morbidity and is characterized by local envenoming and less commonly coagulopathy and acute renal failure. Currently there are three nominal species of this genus: H. hypnale, H. zara and H. nepa. This study investigates the biochemical and pharmacological properties of the venoms from the three Hypnale species in Sri Lanka. The three Hypnale venoms had similar chromatographic profiles using reverse phase high performance liquid chromatography and fractions with procoagulant activity were identified. Hypnale venoms had potent cytotoxicity in cultured rat aorta smooth muscle cells with similar IC50 values. The venoms had weak neurotoxic and myotoxic activity in the isolated chick biventer muscle preparation. They had mild procoagulant activity with close MCC5 values and also phospholipase activity. Locally available polyvalent antivenom did not neutralise any venom effects. The study demonstrates that the three Hypnale venoms are similar and cytotoxicity appears to be the most potent effect, although they have mild procoagulant activity. These findings are consistent with clinical reports

The role of Serum NT-proBNP for predicting left ventricular systolic dysfunction in hospitalized patients in Sri Lanka

Background/aimsOnly a few studies have addressed the role of NT-proBNP in identifying Left Ventricular Systolic Dysfunction (LVSD) in South Asian populations. Therefore, the current study was aimed at assessing the use of serum NT-proBNP in predicting LVSD in a hospitalized population in Sri Lanka.MethodsA random sample of 278 individuals referred for echocardiography at a major Teaching Hospital consented for venous blood samples to be collected for serum NT-proBNP assay by sandwich ELISA. Based on the ejection fraction (LVEF) and fractional shortening (FS), participants were differentiated as LVSD (LVEF<50%, FS≤ 29%) and non-LVSD individuals (LVEF>60%). According to inclusion/exclusion criteria, the final study sample consisted of 100 LVSD patients and 41 non-LVSD individuals.ResultsThe mean ages of the LVSD and non-LVSD groups were 69.1 (±6.2 years) and 71.4 (±2.4 years) (p=0.066) respectively. The median NT-proBNP value (with IQR) among LVSD patients (528.2 pg/mL,355.2–924.2) was comparatively higher than that of non-LVSD individuals (207.3 pg/mL,177.5–343.0). Strong correlations of NT-proBNP level with LVEF (Spearman rho= -0.84, p<0.001) and FS (rho= -0.81, p<0.001) suggested that serum NT-proBNP concentration increases in parallel to deteriorating left ventricular functions. The AUROC of serum NT-proBNP for differentiating LVSD was 0.859 (95% CI:0.79 – 0.92) and the optimal cut-off level for predicting LVSD was 265pg/mL, with 90% sensitivity and 70% specificity.ConclusionCurrent Sri Lankan study revealed a considerable correlation of serum NT-proBNP level with LVSD and utilizing such an assay for screening will facilitate adequate evidence to rule-out LVSD among high-risk residents

Filter based methods for statistical linear inverse problems

Ill-posed inverse problems are ubiquitous in applications. Understanding of algorithms for their solution has been greatly enhanced by a deep understanding of the linear inverse problem. In the applied communities ensemble-based filtering methods have recently been used to solve inverse problems by introducing an artificial dynamical system. This opens up the possibility of using a range of other filtering methods, such as 3DVAR and Kalman based methods, to solve inverse problems, again by introducing an artificial dynamical system. The aim of this paper is to analyze such methods in the context of the linear inverse problem. Statistical linear inverse problems are studied in the sense that the observational noise is assumed to be derived via realization of a Gaussian random variable. We investigate the asymptotic behavior of filter based methods for these inverse problems. Rigorous convergence rates are established for 3DVAR and for the Kalman filters, including minimax rates in some instances. Blowup of 3DVAR and a variant of its basic form is also presented, and optimality of the Kalman filter is discussed. These analyses reveal a close connection between (iterated) regularization schemes in deterministic inverse problems and filter based methods in data assimilation. Numerical experiments are presented to illustrate the theory

Paediatric snakebite envenoming: the world's most neglected 'Neglected Tropical Disease'?

Snakebite disproportionally affects children living in impoverished rural communities. The WHO has recently reinstated snakebites on its list of Neglected Tropical Diseases and launched a comprehensive Strategy for the Prevention and Control of Snakebite Envenoming. In the first of a two paper series, we describe the epidemiology, socioeconomic impact and key prevention strategies. We also explore current challenges and priorities including the production and distribution of safe and effective antivenom.Revisión por pare

Two snakebite antivenoms have potential to reduce Eswatini’s dependency upon a single, increasingly unavailable product: Results of preclinical efficacy testing

Background Snakebite is a major public health concern in Eswatini, where treatment relies upon one antivenom—SAIMR Polyvalent. Although effective in treating snakebite, SAIMR Polyvalent is difficult to source outside its manufacturing country (South Africa) and is dauntingly expensive. We compared the preclinical venom-neutralising efficacy of two alternative antivenoms with that of SAIMR Polyvalent against the lethal and tissue-destructive effects of venoms from five species of medically important snakes using in vivo murine assays. The test antivenoms were ‘Panafrican’ manufactured by Instituto Clodomiro Picado and ‘PANAF’ manufactured by Premium Serums & Vaccines. Principal findings In vivo murine preclinical studies identified both test antivenoms were equally or more effective than SAIMR Polyvalent at neutralising lethal and tissue-destructive effects of Naja mossambica venom. Both test antivenoms were less effective than SAIMR Polyvalent at neutralising the lethal effects of Bitis arietans, Dendroaspis polylepis, Hemachatus haemachatus and Naja annulifera venoms, but similarly effective at neutralising tissue damage induced by B. arietans and H. haemachatus venoms. In vitro immunological assays identified that the titres and toxin-specificities of immunoglobulins (iGs) in the test antivenoms were comparable to that of SAIMR Polyvalent. Plasma clotting disturbances by H. haemachatus and N. mossambica were neutralised by the test antivenoms, whereas SAIMR Polyvalent failed to neutralise this bioactivity of N. mossambica venom. B. arietans SVMP activity was equally reduced by all three antivenoms, and H. haemachatus and N. mossambica PLA2 activities were neutralised by all three antivenoms. Conclusions While both Panafrican and PANAF antivenoms exhibited promising preclinical efficacies, both were less poly-specifically effective than SAIMR Polyvalent in these murine assays. The efficacy of these antivenoms against the lethal and tissue-destructive effects of N. mossambica venom, the most common biting species in Eswatini, identify that Panafrican and PANAF antivenoms offer effective alternatives to SAIMR Polyvalent for the treatment of snakebite in Eswatini, and potentially for neighbouring countries

Investigation of the coagulant effects of Sri Lankan snake venoms and the efficacy of antivenoms

Research Doctorate - Doctor of Philosophy (PhD)Coagulopathy is the commonest systemic effect of snake envenoming. Despite this there is limited information on the severity and time course of venom-induced consumption coagulopathy (VICC) and the effect of antivenom. Evidence of the efficacy and effectiveness of antivenom is vital to continue antivenom treatment for envenoming. There is increasing evidence that early administration of antivenom is essential, but there is a lack of diagnostic tests of envenoming that can be used to decide on antivenom administration. The broad aim of this project was to investigate the procoagulant effects of Sri Lankan snake venoms, and the efficacy and effectiveness of antivenoms against these effects. In addition, the study aimed to explore novel methods of testing for envenoming and for the presence of venom in blood. Snake envenoming cases in Sri Lanka were used with the collection of serial clinical and laboratory data, and blood samples from patients admitted to hospitals in Sri Lanka. Coagulopathy from hump-nosed pit viper and Russell’s viper envenoming was investigated by analyzing citrated samples from envenomed patients. Identification of the snake species was by venom specific sandwich enzyme immunoassay (EIA). Antivenom efficacy was assessed in a series of <i>in-vitro</i> and <i>in-vivo</i> animal studies. Antivenom effectiveness was assessed by undertaking two systematic reviews: Cochrane review of placebo randomized controlled trials and a systematic review of prospective and other controlled trials of antivenom for VICC. The results provide a much better description of VICC using clotting times and factor levels in both hump-nosed pit viper and Russell’s viper envenoming, showing prolonged clotting times and different factor deficiencies. Phospholipase A₂ enzyme levels were investigated as a diagnostic test for snake envenoming and will be key to improving outcomes in snake bite cases as it will allow early identification of envenomed patients so antivenom can be given when it is most effective. The efficacy of two Indian antivenoms was assessed, which showed one to be more efficacious but more importantly explored the difference between lethality studies and clinically focused <i>in vitro</i> studies. Two systematic reviews and antivenom for VICC revealed a lack of placebo controlled randomized trials, but that some comparative clinical trials and observational studies provide information on the effectiveness of antivenom

Current treatment for venom-induced consumption coagulopathy resulting from snakebite

Venomous snakebite is considered the single most important cause of human injury from venomous animals worldwide. Coagulopathy is one of the commonest important systemic clinical syndromes and can be complicated by serious and life-threatening haemorrhage. Venom-induced consumption coagulopathy (VICC) is the commonest coagulopathy resulting from snakebite and occurs in envenoming by Viperid snakes, certain elapids, including Australian elapids, and a few Colubrid (rear fang) snakes. Procoagulant toxins activate the clotting pathway, causing a broad range of factor deficiencies depending on the particular procoagulant toxin in the snake venom. Diagnosis and monitoring of coagulopathy is problematic, particularly in resource-poor countries where further research is required to develop more reliable, cheap clotting tests. MEDLINE and EMBASE up to September 2013 were searched to identify clinical studies of snake envenoming with VICC. The UniPort database was searched for coagulant snake toxins. Despite preclinical studies demonstrating antivenom binding toxins (efficacy), there was less evidence to support clinical effectiveness of antivenom for VICC. There were no placebo-controlled trials of antivenom for VICC. There were 25 randomised comparative trials of antivenom for VICC, which compared two different antivenoms (ten studies), three different antivenoms (four), two or three different doses or repeat doses of antivenom (five), heparin treatment and antivenom (five), and intravenous immunoglobulin treatment and antivenom (one). There were 13 studies that compared two groups in which there was no randomisation, including studies with historical controls. There have been numerous observational studies of antivenom in VICC but with no comparison group. Most of the controlled trials were small, did not use the same method for assessing coagulopathy, varied the dose of antivenom, and did not provide complete details of the study design (primary outcomes, randomisation, and allocation concealment). Non-randomised trials including comparison groups without antivenom showed that antivenom was effective for some snakes (e.g., Echis), but not others (e.g., Australasian elapids). Antivenom is the major treatment for VICC, but there is currently little high-quality evidence to support effectiveness. Antivenom is not risk free, and adverse reactions can be quite common and potentially severe. Studies of heparin did not demonstrate it improved outcomes in VICC. Fresh frozen plasma appeared to speed the recovery of coagulopathy and should be considered in bleeding patients

FIGURE 2. A in Redescription of Pethia melanomaculata (Teleostei: Cyprinidae) from Sri Lanka

FIGURE 2. A, left dentary (buccal view; CP, coronoid process; AA, anguloarticular); B, left premaxilla (dorsal view); C, left maxilla (buccal view; PP, palatine process); D, left infraorbitals 3+4 (lateral view); E, 5th ceratobranchial: of Pethia melanomaculata (WHT 11066, 32.8 mm SL), P. punctata (WHT 11078, 34.9 mm SL) and P. ticto (WHT 11054, 37.0 mm SL). Scale bar: 1 mm