Monday, 3 April 2017

The blog of a rural doctor: understanding snakebite reality in India


Dr. Jeevan and Angel, his wife
Many days since for several reasons I was not posting anything!. Coming back again, I was not sure were to continue. Have so many topics!. Finally decided to write on the blog of a rural doctor, Dr. Jeevan Kuruvilla. He is from Kerala but stablished in Jharkhand state, close to West Bengal. He is working in a rural area and started writing a blog, "The learner", a few years back. But last year there was only one post, and today I've found four more posts in the present year. Good news! I had the feeling he was kind of exhausted and was feeling very sorry for the situation. 



Many hours of hard work and duty, many patients, few resources, many people arriving in extreme conditions due cultural beliefs, misinformation and poverty. Many fake healers and on the last times a deterioration of the political environment and safety due to the insurgence of the naxalite conflict...

The blog is about the cases that reach the 
Dahlias is Barsati's garden
hospital and the everyday life there... deliveries, surgeries, and many, many snakebites. Most of them from krait. 
It wasn't until I came across this blog that I could not see which is day by day reality on snakebites (or the very painful maternal deaths between others...but this is another topic). A mixture of sadness and admiration for those anonymous heroes that deal with them on a daily basis, trying to improve rural health conditions. 

He is posting some nice pictures of roses and other flowers growing in the garden, about his family or nice cake recipes too!

Without pretending, Dr. Jeevan Kuruvilla is giving a lecture on snakebite clinics and treatment, how an old ventilator can save many lives... or how quacks make things much more difficult...
I'm happy he is coming back to write and is giving signs of life again! Wrote him asking for permission to use some of his blog post on snakebites to present in here. Wish he answers.

Here is the link:
http://jeevankuruvilla.blogspot.in



Look what I've found!!!

Toxicol Int. 2015 Jan-Apr; 22(1): 77–82. PMCID: PMC4721181 
doi: 10.4103/0971-6580.172263
Clinico-epidemiological Profile of Snake Bites over 6-year Period from a Rural Secondary Care Centre of Northern India: A Descriptive Study
Shubhanker Mitra, Abhinav Agarwal,1 B. U. Shubhankar,1 Sahil Masih,1 Viswajit Krothapalli,1 Brian Mark Lee,1 Jeevan Kuruvilla,2 and Reginald Alex

Department of Accident and Emergency Medicine, Christian Medical College, Vellore, Tamil Nadu, India
1Department of Medicine, Christian Medical College, Vellore, Tamil Nadu, India

2Consultant in Department of Medicine, Nav Jivan Hospital, Stabarwa, Jharkhand, India


Copyright : © Toxicology International
This is an open access article 
PLEASE, ALWAYS REFER TO THE ORIGINAL ARTICLE.


Abstract
Estimated deaths due to snake bites are more than 46,000 annually in India. Ninety-seven percent bites occur in rural areas. Data on snake bites from Jharkhand rural area are sparse. This study describes 6 years profile of snake bite patients from January, 2007 to December, 2012 at Nav Jivan Hospital in Palamu district, Jharkhand.
Keywords: Anti-snake venom, epidemiology, mortality, snake bite


INTRODUCTION
Three hundred and fifty-six patients were enrolled for this study. There has been a 3.5-fold increase in the number of cases over 6 years. 81.4% of the snake bite patients were younger than 40 years of age without any significant gender-wise difference. Krait is the most common identified species. The peak incidence (40.8%) of the snake bite cases occurs in July and August (at the onset of the monsoon rainfall) rather than entire rainy months. More than 50% patients presented within 5 h of bite. Foot, leg, and hand sites contribute 93.6% of bite. 42.5% had coagulopathy. 49.5% were administered up to five vials of anti-snake venom (ASV) only. 5.4% patients died, and 5.6% patients were referred to higher centers. The death rate was significantly higher among those presented beyond 5 h (64.7% vs. 35.3%) (P = 0.015, odd ratio [OR] 2.7) which was in turn associated with the distance of residence from the hospital. There was no significant difference in mortality with a dose of ASV or among either gender. 10.8% patients developed an allergic reaction to ASV. Pheniramine and hydrocortisone prophylaxis significantly decreased the ASV allergic reaction (absolute risk reduction [ARR] =15.6; number needed to treat [NNT] = 7.4). Expenditure on ASV (median = Rs. 4444) almost equaled that of other medicines (Rs. 4423). 


Context
Snake bite is a major public health problem in India. According to the “million death” study, the estimated annual death due to snake bite in the year 2001–2003 ranged from 40,900 to 50,900 with the mortality rate being higher in the rural areas (4.8–6.0/100,000). Bihar had the third highest annual snake bite related deaths (4500 annually) and the death rate in the state of Jharkhand alone was 1000/year. At the same time, the Indian Government's official figure shows national death rate below 2000 deaths/year. Thus, there is remarkable under-reporting of the snake bite related deaths. There is a paucity of data on snake bite and related events, the cost of care in the snake bite management despite being a major public health problem in India.
Of the four medically important poisonous families of snakes (Elapidae, Viperidae, Atractaspidinae, Colubridae), the Viperidae (viper) and the Elapidae (Cobra and common Krait) remain the most common species of snakes responsible for most of the envenomation in Indian subcontinent.


Aims
We conducted this retrospective descriptive study in a secondary care rural hospital in the Palamu district of Jharkhand to describe the various epidemiological, clinical features, outcome, and cost of care related to snake bite over a period from 2007 to 2012.


Settings and design
Nav Jivan Hospital (NJH) is a charitable, secondary care 100 bedded hospital located at Satbarwa village in the block of Daltonganj in the district of Palamau of Jharkhand, lying about 165 km from the state capital of Ranchi. NJH is run by a team of 6 medical doctors, 1 dentist, 1 ophthalmologist, and department of nursing services. It serves a population of >60 km radius (mainly Palamau and Latehar districts). The hospital has 6 bedded acute medical care unit (AMCU).
The Palamau district spans over 5043 km2 and lies between 23° 50' and 24° 8' North latitude and between 83° 55' and 84° 30' East longitude. Old Palamau district is divided into three districts: (1) Palamau, (2) Garhwa, (3) Latehar. As per the government estimates, the total rural population of Daltonganj is 92,078 in 15,419 household.

Population
All the patients (irrespective of age) presented with the alleged history of any bites between the year January, 2007 and December, 2012 were screened from the inpatient register. The patients who received the discharge diagnosis of “snake bite” based on the documentation of fang marks at the alleged site of envenomation with or without oozing of the blood as confirmed by the attending physician were enrolled in the study. The patients not fulfilling the above criteria or those with confirmed bite by any other organism (e.g., lizard) were excluded. 


MATERIALS AND METHODS
The external Institutional Review Board and Ethics Committee of the EHA approved the study. Since this was a retrospective study and did not involve the disclosure of any individual patient identity, the consent was waived.
The inpatient and AMCU registers from January, 2007 to December, 2012 were screened for collecting the patient's registration number and diagnosis of any bite. The cases where the final diagnosis was other than snake bite were excluded. 
The inpatient records were reviewed, and the data on clinical and epidemiological details were entered in the database. 
The data on cost of ASV, cost of other medications, and other non-medical expenses (including charitable discount, bed and nursing charges) were extracted from the hospital's electronic database. The patients who had inadequate or unclear documentation of more than 20% of the variables were also excluded from the study. In order to eliminate any errors in data collection and entry, the data were double-checked and verified by another independent group.


Statistical analysis used
Statistical analysis was performed using Statistical Package for the Social Science (SPSS) software for Windows Version 16.0. Chicago, SPSS Inc.(released in 2007). Descriptive data are given as mean (standard deviation [SD]) or as median (range). Chi-square test or Fisher exact test was used to compare dichotomous variables and t-test or Mann–Whitney test was used for continuous variables as appropriate. The differences between the two groups were analyzed by univariate analysis and their 95% confidence intervals (CI) were calculated. For all tests, a two-sided P <</i> 0.05 was considered statistically significant. The median cost of care was expressed in Indian rupees.


RESULTS
Epidemiological profile
Demographic details and trend analysis 
From January 2007 to December, 2012, a total of 356 patients were enrolled for this study. As compared to 34 cases in 2007, there has been a 3.5-fold increase in the number of cases by 2012. The median age was 30.0 years (SD 15.4 years). 81.4% of the snake bite incident occurred among people <40 years of age. There was no difference in the gender-wise occurrence of snake bite and the trend over the 6 years period remained the same.

Table-1 Demographic data
 Seasonal variation of the snake envenomation cases 
Over the 6-year period, the peak incidence of the snake bite occurred around the month of July and August, which corresponds to the onset of the monsoon rainfall. It is noteworthy that the incidence of snake bite is not uniform across the monsoon rainy months. Most of the snake bite cases (40.8%) occur over the first 2 months after the onset of monsoon and then nearly halves (21.8%) over the next two rainy months of the monsoon season September and October.
Figure 1 - Seasonal variation of snakebite envenomation cases
District-wise distribution and delay in presentation of the cases
NJH is located in Palamau district of Jharkhand. Although 75% of the snake bite cases are from the Palamau district, the remaining 25% cases are from the adjacent districts of Latehar and Garhwa. More than 60% of the patients from the villages in Palamau and Latehar districts presented within first 5 h of the snake bite as compared to <10% of the patients from farther located villages of Garhwa and other districts (χ2 < 0.01, OR = 2.7, 95% CI: 0.9–7.5). This is attributable to the limited access to the transportation and seeking the advice of local village non-medical practitioners.
Figure 2 - District-wise distribution and delay in presentation (n=325)
Clinical profile

Alleged snake species:
Of 356 case records, documentation on the identification of snake was available in 354 cases. 222 cases confirmed the species of the snake correctly. Krait (33.9%) and viper (25.7%) were the most frequent alleged snake species. Cobra attributed only 3.1% of the alleged confirmed cases.
However, in more than one-third of the cases, the snake species could not be identified. A minority (1.1%) of the snake bite was due to nonpoisonous snake species (see table-1).


Site of bite:
Body mapping of the distribution of the snakebites
The distribution of the site of bite was available on 265 patients. The most common sites being foot (48.3%) and hand (24.2%). The bite in the foot and leg was mainly due to an accidental encounter with the snake during farming work and night expedition in dark especially during the onset of monsoon rains. The bite in the hand, especially among women, was due to domestic exposure to the storage places of organic bio-fuel. The head, neck, and trunk bites were mainly due to the practice of sleeping on the floor.



Clinical manifestations of snakebite envenomation
Local site inflammatory signs:
The local site envenomation features were considered if there was erythema, swelling, and tenderness present at the site of fang marks. Of 346 patients, 171 (49%) had local features of skin and soft tissue inflammation and was most common with viper bite (43.3%).
Ptosis:
Ptosis was common among the Krait and Cobra species (54.2% and 36.4%, respectively). However, it is interesting to note that 5 (5.5%) patients with viper bite and 9 (7%) patients with unidentified snake species also had ptosis.
Respiratory distress:
Respiratory distress was defined when the patient complained of dyspnea, clinical examination revealed tachypnea and auscultation showed either rhonchi or crepitations and pulse oximeter saturation was <95% on room air. Data were available on 314 patients. Cobra and Krait bite were associated most commonly with the respiratory distress (27.3% and 25.8%, respectively).
Coagulopathy: 
The presence of coagulopathy was considered if there was documented bleeding manifestations like gum or nose bleed, hematuria, or malena (excluding the bleeding at the site of fang mark). At NJH, whole blood clotting time (WBCT) is routinely done as an objective measurement of coagulopathy. Results of 327 patients were available for the analysis. Clotting time exceeding 8 min was considered abnormal. If more than one clotting time is performed on one patient, then the highest value was considered to be the most abnormal and the value (in minutes) was recorded for analysis. 
For the analysis, the WBCT was divided into three groups:First group where clotting time was up to 8 min (normal clotting time, suggesting no coagulopathy); second group where clotting time was between 8 and 15 min (suggestive of mild coagulopathy); third group was when clotting time exceeded 15 min.
About 42.5% of the patients had clotting time exceeding 8 min (Group II and Group III). Among the patients with coagulopathy, the majority had clotting time in Group II, suggesting that most patients had minor coagulopathy. Viper and Krait bite were the two most common snake species causing most of the coagulation alteration. It is interesting to observe that among the unidentified snake species bite, more than two-third had deranged clotting time.

Anti-snake venom treatment 
The data on the dosage of ASV were available for 308 patients. 
102 (63.4%) patients with normal WBCT were administered <5 vials of ASV based on local features of envenomation, signs of neurotoxicity, and standard operating procedure. 80 (59.3%) patients with mild coagulopathy were treated with up to 10 vials of ASV. 
Number of ASV used

Outcome 
Of 353 patients, 

  • 280 (79.3%) patients were treated successfully, 
  • 19 (5.4%) expired, 
  • 20 (5.7%) were discharged against medical advice while 
  • 34 (9.6%) were referred to higher center for dialysis or surgical intervention. 
In bivariate analysis, the mortality was significantly lower (P = 0.04, OR 2.7, 95% CI = 0.9–7.5) among those who presented within 5 h of the snake bite. There was no significant difference in the mortality among patients who were treated with low dose versus high dose of ASV (P = 0.11). 

Data on ASV-induced anaphylaxis were available on 241 patients. 
Twenty-six (10.8%) patients developed anaphylactic reaction to ASV 
Comparison of pheniramine (avil) and Hydrocortisone in prophylaxis of ASV reaction
When the event of the anaphylactic reaction was compared among the patients who received Pheniramine and hydrocortisone prophylaxis before or at the time of administration of ASV and those who did not receive the prophylaxis, the incidence of any grade of anaphylactic reaction was significantly lower among those who received Pheniramine and hydrocortisone prophylaxis (ARR = 13.6; NNT = 7.4). 

The median cost of the ASV was Rs. 4444 per patient while the indirect expenses on other medications and hospital bills were Rs. 4423 per patient. Thus, the cost burden of the ASV was almost 50% of the total cost incurred in the management of snake bite in this hospital. Thus, nearly 80% of the patients could be successfully managed at the secondary care hospital with a low dose of ASV.

DISCUSSION
Snake bite is a major public health hazard and neglected tropical disease in India. Most of the snake bite cases occur in the rural areas and in the monsoon months from June to September. The estimated annual death due to snake bite in India is nearly 50,000 persons. The data on the true burden of the disease, role of polyvalent ASV, incident of ASV anaphylaxis, and treatment outcome from rural set up are scarce. As per the national mortality survey in 2001–2003, approximately 4,500 deaths occur annually in the state of Bihar and ranks third among snake bite related deaths in India. Despite this, there has been a paucity of data from this region.
This is the first large descriptive study on the clinico-epidemiological profile and the treatment outcome of the snake bite cases from a secondary care center of Jharkhand, India. 
Over 6-year period, there has been a 3-fold increase in the snake bite cases at NJH. More than 80% of the snake bite cases belong to younger age group (median = 30.0 ± 15.4 years) representing the working class of the population. We found no difference in the gender-wise occurrence of snake bite during the 6-year period. On analyzing the seasonal variability of the snake bite cases, we found that more than 60% of the cases occur during the monsoon months (July–August). 
The interesting difference noted in this study is that most of the snake bite cases (40.8%) occur over the first 2 months after the onset of monsoon and then approximately halves (21.8%) over next two rainy months of the monsoon season. This could be explained by the fact that rainfall at the onset of monsoon disrupts the snake habitat and leads to more accidental contact with a human, both at field work and household. The gender and seasonality pattern of the snake bite cases are similar to other studies from India.
About 75% of the cases are from the Palamau district while remaining 25% cases are from the adjacent districts of Latehar and Garhwa. This could be due to the referral bias as this is the only secondary care hospital which caters continuous care at a subsidized rate to all medical cases. Among the patients from the villages in Palamau and Latehar districts, more than 60% presented within first 5 h of the snake bite but significantly lesser number of patients located in the farther villages of Garhwa and other districts could present to NJH within 5 h (Chi-square <0.01). This is attributable to two main social reasons; viz limited access to the transportation and the practice of receiving first treatment from the local village non-medical practitioners prior to presentation to the hospital.
Krait and viper were the most frequent alleged snake species. 
Foot and hand accounted for nearly three-fourth of the sites of snake bites. Local features of envenomation and coagulopathy were present in nearly half of the patients while ptosis and respiratory distress were present among 24% and 11%, respectively. 

The overall observed mortality was around 5% and significantly higher among those who presented beyond 5 h of envenomation. This was among those who stayed in the districts of Garhwa and farther. More than 80% of the cases were successfully treated with low dose of ASV at the secondary care hospital, and fewer than 10% needed a referral to tertiary care center. This is consistent with most other described studies from India.
The majority of the cost incurred in the patient care is spent on ASV. The prophylactic administration of pheniramine and hydrocortisone prevents ASV hypersensitivity reactions significantly. Thus, with low dose ASV and prophylactic pheniramine and hydrocortisone administration, the majority of the snake bite cases in rural set up can be successfully managed. 
Further randomized trials are warranted on the dose of polyvalent ASV in various toxidromes and the role of anti-histaminics and steroids in the management of snake bite cases in India.

CONCLUSIONS
Snake bite is a neglected tropical disease in India. The majority of the cases occur in the younger adults and at the onset of the rainy season with equal gender distribution in rural areas in Jharkhand. Krait and viper remain the most common alleged snake species. Most of the cases can be managed successfully at a secondary care set up and a low dose of polyvalent ASV. The morbidity and mortality increase with the delay in presentation to the hospital, which in turn depend on the social beliefs and practices. The incidence of ASV related anaphylactic reaction can be decreased significantly by prophylactic administration of hydrocortisone and pheniramine. Expenditure on ASV constitutes a large proportion of total bill.





Nice! Lots of hard work in only a few pages and none of the emotional, human aspects of all the people affected (the patient, the family, the health workers...) are reflected on the scientific papers... 
We need studies on the social, emotional, human impact of snakebites.


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





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.