Saturday 11 February 2017

Bothrops asper: the lethal velvet

The last three post were related to the 45th anniversary of the "Instituto Clodomiro Picado", Costa Rica. The TV program "ConCiencia" (that can be read as WithScience and also as Consciousness) consisting on two interviews by Mr. Gustavo Gutiérrez Espeleta: first to Dr. José Mª Gutiérrez, investigator of the ICP and professor of the Faculty of Microbiology at the University of Costa Rica and second, to Dr. Alberto Alape-Girón, the actual director of the Instituto. 
All the research done by Dr. Clodomiro started early last century. He was worried about the high number of deaths happening on the laborers, mostly in the banana plantations, due to snakebites. From the interview we know that the "Serpiente Terciopelo" (Velvet snake, Lance-head, Fer-de-Lance) Bothrops Asper, is most common snake, far away in number of envenomations from other snakes, responsible for those lethal envenomations. So, even if we are far away from that country, I would like to dedicate this post to know more about this snake.
In all North, Central and South América, the predominant venomous snakes are pit vipers. The only elapid that can be found in the Coral snake, also deathly venomous, but the number of bites is relatively low compared to pit-vipers.

Bothrops Asper:
This is the information we can get from the reptile database: 
Bothrops Asper, (Garman, 1883)
There is a kind of overlaping between the Bothrops Asper (B. Asper) and the Bothrops Atrox (B. Atrox), that made even in the fifties that this B. Asper was called B. atrox-asper by some herpetologist. 

Distribution:

S Mexico (Chiapas, Oaxaca, Veracruz, Puebla, Quéretaro, Hidalgo, San Luis Potosí, Hidalgo, Tamaulipas southwards), Guatemala, Honduras, Nicaragua, Costa Rica, Panama, Belize, Colombia (Valle del Cauca), W Ecuador, Venezuela; elevation (Honduras): 880-1160 m, 0-1500 m (Colombia).
(B. Atrox is found in South America only, not in Central America. Common names for B. Atrox are Barba amarilla, Fer-de-lance and common lancehead). In some countries as Colombia, both species coexist. 

Bothrops Asper




Named after Latin “asper” = rough, in reference to the nasty temper of the snake, or to the roughness of the keeled scales on the dorsum. 









Toxicon, Vol 54, Issue 7
Special issue: Bothrops asper,
from natural history to public health


Natural history of the terciopelo Bothrops asper (Serpentes: Viperidae) in Costa Rica
Toxicon, Vol 54, Issue 7, Pages 904–922
Mahmood Sasa, Dennis K. Waskob, William W. Lamarc
Instituto Clodomiro Picado, Universidad de Costa Rica, San José, Costa Rica 
Department of Biology, University of Miami, Coral Gables, FL 33124 USA
Department of Biology, The University of Texas at Tyler, TX 75799, USA

Abstract 
The terciopelo Bothrops asper is the only lancehead species widely distributed in the humid lowlands of Middle America and northwestern South America. Its large body size, relative abundance and cryptic habits contribute to the high incidence of snakebites induced by this species throughout its distribution. The terciopelo plays an important role in ecosystems, both as prey and as a generalist predator. Diet comprises a great variety of prey items, including some species that are considered nuisances. B. asper, as other lancehead species, exhibits a notable ontogenetic shift in diet, consuming ectotherms (mainly frogs and lizards) when young, and increasingly incorporating birds, rodents, and other small mammals with maturity. Adult terciopelos also consume large anurans, especially when endothermic prey availability is low. 
Using radiotelemetry we determined home range and movement patterns from 28 individual B. asper at La Selva Biological Station, Costa Rica. Overall home range estimates are relatively small compared with other pitvipers, averaging between 3.71 ha and 5.95 ha; home range size did not differ between males and females. Movement patterns are largely aseasonal and consist of short (<10 m) movements between daytime shelter and nocturnal ambush sites within a given area, interspersed with longer distance (>50 m) movements to new foraging areas. Habitat use is related to prey availability and therefore to foraging strategy. Our data support a strong preference for areas near swamps by both sexes. 
Reproduction in B. asper is highly seasonal, and – apparently – biannual. Reproductive cycles in Costa Rica are tightly related to rainfall patterns. Therefore, the timing of breeding differs between populations in the Caribbean and Pacific lowlands. Bothrops asper is adapted to areas with low levels of disturbance along the agricultural frontier, and consequently it is not rare to find it in or near human dwellings. However, despite popular belief, no evidence supports a purported increase in population density of this species in Costa Rica. Despite human persecution and substantial modification of habitat, B. asper is a species with a conservation status of least concern, and probably will likely persist well into the future. Thus, it is important to learn how to coexist with this species, and to improve mechanisms for the prevention and treatment of accidental snakebite and its consequences. 


Epidemiological, clinical and therapeutic aspects of Bothrops asper bites
Toxicon, Vol 54, Issue 7, 1 December 2009, Pages 998–1011
Rafael Otero-Patiño,
Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
http://dx.doi.org/10.1016/j.toxicon.2009.07.001

Abstract
Bothrops asper inflicts the majority of snakebites in Central America and in the northern regions of South America, mostly affecting young agricultural workers in rural settings. This species is capable of provoking severe envenomings associated with local and systemic manifestations. The main clinical features are: 
  • local edema, 
  • ecchymoses, blisters, dermonecrosis, 
  • myonecrosis, 
  • defibrinogenation, thrombocytopenia, systemic bleeding, 
  • hypotension and renal alterations. 
  • In addition, soft-tissue infection, acute renal failure, compartmental syndrome, central nervous system hemorrhage and, in pregnant women, abortion, fetal wastage and abruptio placentae have been described as complications. 
Intravenous administration of antivenom constitutes the mainstay in the therapy. Antivenoms composed of either whole IgG or F(ab′)2 fragments, manufactured in Brazil, Colombia, Costa Rica and Mexico, have been tested in controlled clinical trials, and rational protocols for antivenom administration have been developed. In addition to antivenom therapy, a number of ancillary interventions are recommended in the treatment of B. asper bites.


Studies on the venom proteome of Bothrops asper: Perspectives and applications 
Toxicon, Vol 54, Issue 7, 1 December 2009, Pages 938-948
Alberto Alape-Girón, Marietta Flores-Díaza, Libia Sanzd, Marvin Madrigal, José Escolano, Mahmood Sasa, Juan J. Calvete.
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica
Departamento de Bioquímica, Escuela de Medicina, Universidad de Costa Rica
Centro de Investigaciones en Estructuras Microscópicas, Universidad de Costa Rica,
Instituto de Biomedicina de Valencia, C.S.I.C., Jaume Roig 11, 46010 Valencia, Spain

Abstract
Bothrops asper is responsible for the vast majority of snakebite accidents in Central America and several studies have demonstrated that specific toxic and enzymatic activities of its venom vary with the geographic origin and age of the specimens. 
Variability in venom proteins and enzymes between specimens from the Caribbean and the Pacific versants of Costa Rica has been reported since 1964. Recently, we performed a comparative proteomic characterization of the venoms from one population of each versant. Proteins belonging to several families, including 
  • Disintegrin, 
  • Phospholipases A2, 
  • serine proteinases, 
  • C-type lectins, 
  • CRISP, 
  • L-amino acid oxidase, and 
  • Zn2+-dependent metalloproteinases 
show a variable degree of relative occurrence in the venoms of both populations. The occurrence of prominent differences in the protein profile between venoms from adults and newborns, and among venom samples from individual specimens of the same region or developmental stage, further demonstrated the existence of geographic, ontogenetic and individual variability in the venom proteome of this species. These findings provide new insights towards understanding the biology of B. asper, contribute to a deeper understanding of the pathology induced by its venom and underscore the importance of the use of venoms pooled from specimens from both regions for producing antivenom exhibiting the broadest cross-reactivity. Furthermore, knowledge of the protein composition of B. asper venom paves the way for detailed future structure–function studies of individual toxins as well as for the development of new protocols to study the reactivity of therapeutic antivenoms.



There is a beautiful documentary on some Snakes of Costa Rica. The search for the giant lance-head pit viper on the mountains of Costa Rica. 
Austin Stevens: In Search of The Ultimate Pit Viper. 
You can find it easily on Youtube.
Austin Stevens, a wildlife photographer, specialized on snakes receives the assignment to photograph a giant lance-head, the "terciopelo" snake, in Costa Rica. You will see how he treats the snakes and how snakes behave. Some are quite calm, almost do not try to bite like the "cuba" that appears at the beginning. The views of the nature are amazing. In the video you will see very clearly the very brave temperament of the Terciopelo as well as the huge fangs it has! I would like to know from where the name is coming from, as asper means exactly the opposite to velvet... ¿?


This new appeared on the newspaper "La Nación", of Costa Rica, 19 Jan. 2015. Article by Hugo Solano. http://www.nacion.com/sucesos/Mordedura-serpiente-acabo-vida-agricola_0_1464453690.html
Beyond documentaries, snakebites are still a crude reality for many laborers.
Valentino Barrantes, 54 years old died after the bite of a "terciopelo" snake. He was working at the farm when was bitten. Even if he was wearing boots, the fangs of the snake went through them and bite him on the left toe. Another worker went after the snake, kill it and after that runned 1,5 km to the road and looked for the help of the Red Cross. When they arrived, Mr. Barrates was already death.

Important: Do not waste time at avoid putting yourself at risk looking and trying kill the snake responsible of the bite. Put the victim on a safe place and run for help!
Photo of the deceased appeared in "Diario Extra", José Brenes, correspondent

Here is a sadly famous image of the leg of a boy bitten by a Bothrops asper. 

Extensive Tissue Necrosis of the Lower Limb in an 11-Year-Old Boy Who Had Been Bitten Two Weeks Earlier by a B. asper in Ecuador

Only antibiotic treatment had been given, so tissue damage was extensive, requiring above-knee amputation. Such pathological alterations are caused by the direct action of locally acting toxins in the venom (mostly metalloproteinases and phospholipases A2), together with an indirect effect promoted by local inflammatory events and ischemia secondary to venom-induced vascular damage and increased intracompartmental pressure. (Image: D. A. Warrell)





ॐ लोकाः समस्ताः सुखिनो भवन्तु ॥
Om Lokah Samasthah Sukhino Bhavantu
May all beings everywhere be happy and peaceful.




Friday 10 February 2017

(III) Homage to Dr. Clodomiro Picado. 45th years of the Clodomiro Picado Institute.

This is the Third and last part of the program. 
Interviews to the present director of the Instituto Clodomiro Picado, Dr. Alberto Alape-Girón. 

3rd PART
Starts minute 17
https://www.youtube.com/watch?v=f4GQYZKVFkc
P: On the first part we talked partially about the history of the Clodomiro Picado Institute with Dr. José Mª Gutiérrez, on the second part Don José Mª talked about the present reality of the Institute and the reasons behind it has become a research icon and on this third part we do have the pleasant visit of Dr. Alberto Alape-Girón, which is the actual director of Clodomiro Picado as well as investigator and professor of the Faculty of Microbiology, University of Costa Rica.
Thank you so much Alberto to be here with us to talk precisely about the future of the Clodomiro Picado Institute. As the director, could you tell us which are the future Clodomiro Picado goals on research, social action and academic education?

Dr.AAJ: Thank you so much Gustavo for the opportunity, in fact, we traced the road ahead in our second strategic plan that was stated three years ago, when I just took over the direction of the “Instituto” and basically, we will continue with our research related to “ofidismo” incorporating emerging technologies as geographic information systems, studies done at the “Instituto” in collaboration with other investigators allowed for example to draw a map to see in which regions of the country the snakebite accidents are more frequent and how this maps of incidence overlap with the maps related to de access to the medical care, to Primary Health facilities.

J. Venom. Anim. Toxins incl. Trop. Dis vol.20  Botucatu  2014  Epub Mar 06, 2014

Current challenges for confronting the public health problem of snakebite envenoming in Central America
José María Gutiérrez
Figure 3 Incidence of snakebite in Costa Rica per district per 100,000 population (1990-2007). Prepared by Erik Hansson and reprinted from “Using geographical information systems to identify populations in need of improved accessibility to antivenom treatment for snakebite envenoming in Costa Rica” by Hansson et a!., PLOS Neglected Tropica! Diseases, 2013, 7 (1), e2009 [37]. Creative Commons Attribution License (CCAL). 



Figure 4 Distribution of hospitals, clinics and ambulance stations in Costa Rica, and estimated time to reach hospitals or clinics in various regions of the country. As shown in Figure 3, regions where transportation to health facilities takes longer correspond to regions of high snakebite incidence. Prepared by Erik Hansson and reprinted from Hansson et al. [37]. 

This research will enable us to for example to suggest to the Health Authorities how to re-distribute those Health centers or how to develop strategies to care for those patients appropriately. Furthermore, related to the techniques for the study of the venoms and the anti-venom characterization, some years back, the university did an important investment on the Proteomics Laboratory, thanks to which we have been able to characterize virtually all the venoms of the Costa Rica’s snakes. An integral characterization that enabled us to see which are the toxins presents in each venom…

P: of the different snakes…

Dr.AAJ: yes, yes, of the different species… and also to see the “reactivity” of the anti-venoms: which toxins are better recognized by the anti-venom and which toxins are weakly recognized by it, in such a way that those strategies will enable us to “re-formulate” the immunization blend to prepare even more effective anti-venoms.

P: This kind of investigation you are already working on that…

Dr.AAJ: yes, sure, we have been doing it since some years but the impact that those studies will have is something that we will see in a future.
Another aspect that I would like to highlight is the empowerment related to technological research. The section of technological development has been reinforced, both with professionals and equipment, giving as result really important scientific advances like the production of new anti-venoms for other countries or new anti-venoms that are being developed for other countries…

P: So, the production will increase… in the future…

Dr.AAJ: Production will increase, yes, but… this area of development and technological transfer is like another track that we will be exploring on the next years. For example, an anti-venom was developed to be distributed in Africa, North Africa, which is effective…  another anti-venom for Papua New Guinea and nowadays a new anti-venom to be used in Sri Lanka is under development; in that case, we are exploring a new model of technological transfer because there is a non governmental organization that cooperates with a university of Sri Lanka and they are going to receive the technology to build an anti-venom production plant there (See post on Hypnale Hypnale for complete overview). So, the venom that we are developing for Sri Lanka, will not be produced by us but we are going to transfer the technology for that. In this case, they are covering all the financial cost of the development. As it is a non-profit organization and a university, we do not have any intention to profit but we consider it as an extension outside Costa Rica of our social activity.  
Dr. Alberto Alape Jirón at the Proteomics lab. 
P: Alberto, in Latin America, how many anti-venom production centers do exist?

Dr.AAJ: Well, the main centre is the Butantan Institute in Brazil, other countries... in South America and Mexico, they also have public laboratories that manufacture the anti-venom but on most of the cases, the production is not enough to cover all the needs even on their own country, the local needs, then… there is a private company in Mexico, another private company in Colombia and another private company in Argentina… but in general, we a living a problem of shortage of anti-venom, that it is not that marked in Latin America as it is in  Africa, were this is a major problem. This pathology, the snakebite envenomation, has been declared by the World Health Organization as a Neglected disease, type 3, precisely because the big trans-national pharmaceutical companies are not interested. This is something that affects poor people from poor countries so… many private companies that two decades ago were producing the anti-venom just retired from the market leaving without any supply... in Africa there are hundreds of thousands of people that cannot be attended because there is no anti-venom.
http://www.upi.com/Health_News/2015/09/07/Snake-bite-crisis-Sanofi-Pasteur-to-stop-producing-anti-venom/4711441655970/

Banywich Bone, a teenager from South Sudan, had to have his leg amputated following an infection from a snakebite. Photo by Pierre-Yves Bernard/Doctors Without Borders
P: Because commercially this is not… attractive

Dr.AAJ: Exactly, this is of no interest for them.

P: We have only one and a half minutes to finish and I would like you to talk about the donation you received, very relevant documents, of uniqueness historical value: The Doctorate title Honoris Causa of Don Clodomiro Picado as well as other documents… please tell us what did you received.

Dr.AAJ: We received the original titles that Dr. Clodomiro Picado received in France, the Honoris Cause title that he received from the University of Costa Rica. The donor is Dr. Carlos Roberto Páez, a relative of Dr. Clodomiro Picado’s wife. He had the generosity to donate those highly valuable documents, some of them are more than one century old. The documents were treated and preserved with the aim to be exhibited at the “Instituto”. We are very happy because this donation is coincidental with the 45th Anniversary. It was a nice anniversary gift.  

P: Those historical documents are… can be visited by any person for example listening to us in this moment?
Dr. Clodomiro on the Graduation day at the
Sorbonne University. Paris. 1913

Dr.AAJ: Sure! The documents are in the Auditorium of the “Instituto” and every person willing to see them is welcomed. The “Instituto” is an Open Door institution for general public and we are always ready and always helping people interested on the topic like students…

P: Even there are some extraordinary paintings like Clodomiro holding a “terciopelo” snake…

Dr.AAJ: Yes, another donation was an oil painted fresco of Cloromiro Picado, from 1954 that was restored and is on exhibition too.

P: Thank you very much Alberto I wish you all many congratulations for this 45th anniversary of Clodomiro Picado and much more achievements!





Interesting links:
Link to the Instituto Clodomiro Picado website
http://www.icp.ucr.ac.cr

A blog about the Instituto (in Spanish)
https://plus.google.com/106487061985305087179
ॐ लोकाः समस्ताः सुखिनो भवन्तु ॥
Om Lokah Samasthah Sukhino Bhavantu
May all beings everywhere be happy and peaceful.