Flow diagram of the selection process used in this study.

<p>The search was conducted on 15 September 2014. Merging the search results gave a total of 41 clinical trials investigating the efficacy or safety of snake antivenoms, of which four were active. A total of 36 different antivenoms were investigated (see <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003896#pntd.0003896.t002" target="_blank">Table 2</a>). Based on the trial design (Phase I to IV), ten products were considered still “under development,” although development appears to have stalled for most of them. Our search strategy appears robust; a report conducted in 2010 identified a total of 43 randomized controlled trials on snakebite envenoming, 28 of which investigated antivenom properties [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003896#pntd.0003896.ref011" target="_blank">11</a>]. We retrieved all except two of these trials [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003896#pntd.0003896.ref012" target="_blank">12</a>,<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003896#pntd.0003896.ref051" target="_blank">51</a>]; the discrepancy could be due to differences in the criteria used to define clinical trials.</p

“Broken neck” sign observed in a 14-year-old girl bitten by a Russell's viper in India.

<p>Envenoming by cobras, kraits and—in some areas—by Russell's viper frequently leads to progressive descending paralysis. Looking for the broken neck sign, which is caused by paralysis of the neck flexor muscles, should be part of the routine clinical assessment of patients. In this case, neuroparalysis persisted for five days despite antivenom treatment, but without progression toward respiratory failure. <i>Image credit: H. S. Bawaskar</i>.</p

Characteristics of snake bite victims in South Asia.

<p>Characteristics of snake bite victims in South Asia.</p

Tourniquet on a 43-year-old woman presenting at a rural health post in Nepal.

<p>First-aid methods applied throughout South Asia are largely inadequate. Tourniquets in particular can have deleterious effects. This patient consulted after being bitten by a nonvenomous rat snake (<i>Ptyas mucosa</i>) that she had killed and brought for identification. After reassurance, local treatment, and observation, she was uneventfully discharged from the health post. <i>Image credit: E. Alirol</i>.</p

Available snake antivenom products in sub-Saharan Africa, as of September 2014.

<p>Available snake antivenom products in sub-Saharan Africa, as of September 2014.</p

List of antivenoms investigated in clinical trials published in peer-reviewed journals or on public registries.

<p>¹ Not all publications mentioned the trial phase, and development status was established based on trial design, primary objectives, and number of subjects. This classification, though, bears some limitations, especially with regards to snake antivenoms development, in which Phase I with healthy volunteers are generally not conducted.</p><p>List of antivenoms investigated in clinical trials published in peer-reviewed journals or on public registries.</p

Circumstances of the bite and baseline characteristics of victims of snakebite in southern Nepal between April 2010 and October 2012 (n = 194).

<p>Circumstances of the bite and baseline characteristics of victims of snakebite in southern Nepal between April 2010 and October 2012 (n = 194).</p

Flow diagram showing numbers of individuals screened and included in each study centre.

<p>Between 01/04/2010 and the 31/10/2012, 749 victims of snakebite were included in the study and the snake species responsible for the bite could be ascertained in 194 cases.</p

Clinical features on admission of victims of snakebite in southern Nepal between April 2010 and October 2012 (n=194).

<p>Initial assessment of snakebite victims included vital signs, patients’ complaints and standardized evaluation of envenoming signs.</p

Factors associated with a positive PCR among 565 snake bite victims.

<p>Unadjusted Risk Ratio (RR) and their 95% Confidence Interval (95% CI) were calculated with respect to the baseline category, i.e., absence of the risk factor (RR = 1).</p