Preclinical Evaluation of Caprylic Acid-Fractionated IgG Antivenom for the Treatment of Taipan (Oxyuranus scutellatus) Envenoming in Papua New Guinea

articulo (arbitrado) -- Universidad de Costa Rica, Instituto de Investigaciones Clodomiro Picado, 2011Background: Snake bite is a common medical emergency in Papua New Guinea (PNG). The taipan, Oxyuranus scutellatus, inflicts a large number of bites that, in the absence of antivenom therapy, result in high mortality. Parenteral administration of antivenoms manufactured in Australia is the current treatment of choice for these envenomings. However, the price of these products is high and has increased over the last 25 years; consequently the country can no longer afford all the antivenom it needs. This situation prompted an international collaborative project aimed at generating a new, low-cost antivenom against O. scutellatus for PNG. Methodology/Principal Findings: A new monospecific equine whole IgG antivenom, obtained by caprylic acid fractionation of plasma, was prepared by immunising horses with the venom of O. scutellatus from PNG. This antivenom was compared with the currently used F(ab’)2 monospecific taipan antivenom manufactured by CSL Limited, Australia. The comparison included physicochemical properties and the preclinical assessment of the neutralisation of lethal neurotoxicity and the myotoxic, coagulant and phospholipase A2 activities of the venom of O. scutellatus from PNG. The F(ab’)2 antivenom had a higher protein concentration than whole IgG antivenom. Both antivenoms effectively neutralised, and had similar potency, against the lethal neurotoxic effect (both by intraperitoneal and intravenous routes of injection), myotoxicity, and phospholipase A2 activity of O. scutellatus venom. However, the whole IgG antivenom showed a higher potency than the F(ab’)2 antivenom in the neutralisation of the coagulant activity of O. scutellatus venom from PNG. Conclusions/Significance: The new whole IgG taipan antivenom described in this study compares favourably with the currently used F(ab’)2 antivenom, both in terms of physicochemical characteristics and neutralising potency. Therefore, it should be considered as a promising low-cost candidate for the treatment of envenomings by O. scutellatus in PNG, and is ready to be tested in clinical trials.This study was supported by Vicerrectoría de Investigación, Universidad de Costa Rica (project 741-A9-003); the PNG Office of Higher Education, CTP Limited (Milne Bay Estates), and the Australian Venom Research Unit (University of Melbourne), which is funded by the Australian Government Department of Health and Ageing, the Australia Pacific Science Foundation and Snowy Nominees. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Enteric Pathogens in Stored Drinking Water and on Caregiver's Hands in Tanzanian Households with and without Reported Cases of Child Diarrhea.

Diarrhea is one of the leading causes of mortality in young children. Diarrheal pathogens are transmitted via the fecal-oral route, and for children the majority of this transmission is thought to occur within the home. However, very few studies have documented enteric pathogens within households of low-income countries. The presence of molecular markers for three enteric viruses (enterovirus, adenovirus, and rotavirus), seven Escherichia coli virulence genes (ECVG), and human-specific Bacteroidales was assessed in hand rinses and household stored drinking water in Bagamoyo, Tanzania. Using a matched case-control study design, we examined the relationship between contamination of hands and water with these markers and child diarrhea. We found that the presence of ECVG in household stored water was associated with a significant decrease in the odds of a child within the home having diarrhea (OR = 0.51; 95% confidence interval 0.27-0.93). We also evaluated water management and hygiene behaviors. Recent hand contact with water or food was positively associated with detection of enteric pathogen markers on hands, as was relatively lower volumes of water reportedly used for daily hand washing. Enteropathogen markers in stored drinking water were more likely found among households in which the markers were also detected on hands, as well as in households with unimproved water supply and sanitation infrastructure. The prevalence of enteric pathogen genes and the human-specific Bacteroidales fecal marker in stored water and on hands suggests extensive environmental contamination within homes both with and without reported child diarrhea. Better stored water quality among households with diarrhea indicates caregivers with sick children may be more likely to ensure safe drinking water in the home. Interventions to increase the quantity of water available for hand washing, and to improve food hygiene, may reduce exposure to enteric pathogens in the domestic environment

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Tetrodotoxic poisoning from ingestion of a porcupine fish (Diodon hystrix) in Papua New Guinea: nerve conduction studies.

Near Port Moresby in Papua New Guinea, three of four adult family members who ate a porcupine fish (Diodon hystrix) were severely poisoned. Within one hour of the meal, both the mother and her older daughter had developed paraesthesiae, ataxia, hypersalivation, sweating, and had collapsed and died. The younger daughter developed similar symptoms with progressive paralysis requiring mechanical ventilation for 24 hr, but she made a complete recovery 10 days after the poisoning. In this patient, nerve conduction studies showed reduced sensory and motor conduction velocities and evoked amplitudes with gradual improvement in parallel with the patient's clinical condition, consistent with the known action of tetrodotoxin on voltage-gated sodium channels

Analysis of referral letters to assess the management of poisonous snake bite in rural Papua New Guinea.

A prospective series of patients envenomed after snake bite was seen at Port Moresby General Hospital (PMGH), Papua New Guinea, between January 1991 and December 1992. Referral letters were received with 60 of the patients who had been initially seen at a health centre. These letters were analysed in conjunction with our own clinical observations. The importance of non-clotting blood and local lymphadenopathy as early signs of systemic poisoning did not appear to be universally recognized by staff in health centres. In some cases, no attempt was made to transfer the patient to hospital until signs of neurotoxicity were established with potentially dangerous delay. Analysis of both hospital and health centre records suggests that the majority of deaths which occurred in Central Province, Papua New Guinea, during the period of the study were due to delay in transfer to hospital. We suggest that all patients with unequivocal signs of envenoming in Central Province, Papua New Guinea, should be transferred to PMGH as soon as possible. Antivenom should also be given as soon as possible, but this does not remove the need for immediate transfer

The epidemiology of snake bite in Central Province and National Capital District, Papua New Guinea.

Snake bite is an important medical problem in some areas of Papua New Guinea and appears to be most common in the Central Province and National Capital District. The overall incidence for Central Province is 215.5 per 100,000 population, but Kairuku subprovince has an incidence of 526 per 100,000, which is amongst the highest in the world. The clinical pattern of envenoming also varies within the Province, suggesting that different species of snake may be responsible for bites in different areas. Most envenomed patients are bitten during daylight on the lower limb and are rarely able to describe the snake. The mortality rate in Central Province is 7.9 per 100,000; most patients die from ventilatory failure due to severe neurotoxicity. Mortality might be reduced by increased use of compression bandaging as a first aid measure, earlier treatment with antivenom and earlier referral to hospital

Venom detection kits in the management of snakebite in Central province, Papua New Guinea.

The bites of six species of venomous elapid snakes in Central Province Papua New Guinea produce similar clinical syndromes. Optimal management of envenomed patients involves the use of monospecific antivenom. In this study, Venom Detection Kits (VDKs) (CSL Diagnostics, Melbourne) were used to try to make a specific diagnosis in envenomed patients at their admission. VDKs detected venom in admission bite site swabs from 39 to 46 patients (85%). Thirty-eight of these patients were shown to have been bitten by taipans. In all cases where venom was detected by the VDK, this correlated with subsequent laboratory enzyme immunoassay results. Selective use of VDKs in Central Province could allow more widespread use of monospecific antivenoms and produce considerable financial savings

Failure of 3,4-diaminopyridine and edrophonium to produce significant clinical benefit in neurotoxicity following the bite of Papuan taipan (Oxyuranus scutellatus canni).

Progressive systemic neurotoxicity is a common feature in patients envenomed following the bite of a Papuan taipan (Oxyuranus scutellatus canni). Respiratory paralysis, which commonly results, accounts for considerable morbidity and mortality. Established neurotoxicity does not respond to antivenom. In this study, a combination of clinical and electrophysiological variables was used to assess the effect of edrophonium and 3,4-diaminopyridine in patients with significant neurotoxicity. Both drugs produced minor electrophysiological and clinical changes in envenomed patients. This effect was maximal when the 2 drugs were used in combination, but was insufficient to be of significant clinical benefit. Neither drug can be recommended for use in the management of Papuan taipan bite