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Cost-Effectiveness of Antivenoms for Snakebite Envenoming in 16 Countries in West Africa

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Background: Snakebite poisoning is a significant medical problem in agricultural societies in Sub Saharan Africa. Antivenom (AV) is the standard treatment, and we assessed the cost-effectiveness of making it available in 16 countries in West Africa. Methods: We determined the cost-effectiveness of AV based on a decision-tree model from a public payer perspective. Specific AVs included in the model were Antivipmyn, FAV Afrique, EchiTab-G and EchiTab-Plus. We derived inputs from the literature which included: type of snakes causing bites (carpet viper (Echis species)/non-carpet viper), AV effectiveness against death, mortality without AV, probability of Early Adverse Reactions (EAR), likelihood of death from EAR, average age at envenomation in years, anticipated remaining life span and likelihood of amputation. Costs incurred by the victims include: costs of confirming and evaluating envenomation, AV acquisition, routine care, AV transportation logistics, hospital admission and related transportation costs, management of AV EAR compared to the alternative of free snakebite care with ineffective or no AV. Incremental Cost Effectiveness Ratios (ICERs) were assessed as the cost per death averted and the cost per Disability-Adjusted-Life-Years (DALY) averted. Probabilistic Sensitivity Analyses (PSA) using Monte Carlo simulations were used to obtain 95% Confidence Intervals of ICERs. Results: The cost/death averted for the 16 countries of interest ranged from $1,997 in Guinea Bissau to $6,205 for Liberia and Sierra Leone. The cost/DALY averted ranged from $83 (95% Confidence Interval: $36-$240) for Benin Republic to $281 ($159-457) for Sierra-Leone. In all cases, the base-case cost/DALY averted estimate fell below the commonly accepted threshold of one time per capita GDP, suggesting that AV is highly cost-effective for the treatment of snakebite in all 16 WA countries. The findings were consistent even with variations of inputs in 1-way sensitivity analyses. In addition, the PSA showed that in the majority of iterations ranging from 97.3% in Liberia to 100% in Cameroun, Guinea Bissau, Mali, Nigeria and Senegal, our model results yielded an ICER that fell below the threshold of one time per capita GDP, thus, indicating a high degree of confidence in our results. Conclusions: Therapy for SBE with AV in countries of WA is highly cost-effective at commonly accepted thresholds. Broadening access to effective AVs in rural communities in West Africa is a priority.
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RESEARCH ARTICLE
Cost-Effectiveness of Antivenoms for
Snakebite Envenoming in 16 Countries in
West Africa
Muhammad Hamza
1
, Maryam A. Idris
1
, Musa B. Maiyaki
1
, Mohammed Lamorde
2
, Jean-
Philippe Chippaux
3
, David A. Warrell
4
, Andreas Kuznik
1,2,5
, Abdulrazaq G. Habib
1
*
1College of Health of Sciences, Bayero University, Kano, Nigeria, 2Infectious Diseases Institute, Makerere
University College of Health Sciences, Kampala, Uganda, 3Institut de Recherche pour le Development,
Cotonou, Benin Republic and Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, Paris,
France, 4Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom, 5Celgene
Corporation, Warren, New Jersey, United States of America
*abdulrazaq_habib@yahoo.co.uk
Abstract
Background
Snakebite poisoning is a significant medical problem in agricultural societies in Sub Saha-
ran Africa. Antivenom (AV) is the standard treatment, and we assessed the cost-effective-
ness of making it available in 16 countries in West Africa.
Methods
We determined the cost-effectiveness of AV based on a decision-tree model from a public
payer perspective. Specific AVs included in the model were Antivipmyn, FAV Afrique, Echi-
Tab-G and EchiTab-Plus. We derived inputs from the literature which included: type of
snakes causing bites (carpet viper (Echis species)/non-carpet viper), AV effectiveness
against death, mortality without AV, probability of Early Adverse Reactions (EAR), likelihood
of death from EAR, average age at envenomation in years, anticipated remaining life span
and likelihood of amputation. Costs incurred by the victims include: costs of confirming and
evaluating envenomation, AV acquisition, routine care, AV transportation logistics, hospital
admission and related transportation costs, management of AV EAR compared to the alter-
native of free snakebite care with ineffective or no AV. Incremental Cost Effectiveness
Ratios (ICERs) were assessed as the cost per death averted and the cost per Disability-
Adjusted-Life-Years (DALY) averted. Probabilistic Sensitivity Analyses (PSA) using Monte
Carlo simulations were used to obtain 95% Confidence Intervals of ICERs.
Results
The cost/death averted for the 16 countries of interest ranged from $1,997 in Guinea Bissau
to $6,205 for Liberia and Sierra Leone. The cost/DALY averted ranged from $83 (95% Con-
fidence Interval: $36-$240) for Benin Republic to $281 ($159457) for Sierra-Leone. In all
cases, the base-case cost/DALY averted estimate fell below the commonly accepted
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004568 March 30, 2016 1 / 16
OPEN ACCESS
Citation: Hamza M, Idris MA, Maiyaki MB, Lamorde
M, Chippaux J-P, Warrell DA, et al. (2016) Cost-
Effectiveness of Antivenoms for Snakebite
Envenoming in 16 Countries in West Africa. PLoS
Negl Trop Dis 10(3): e0004568. doi:10.1371/journal.
pntd.0004568
Editor: H Janaka de Silva, University of Kelaniya,
SRI LANKA
Received: October 19, 2015
Accepted: March 2, 2016
Published: March 30, 2016
Copyright: © 2016 Hamza et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
Data Availability Statement: All relevant data are
within the paper and its Supporting Information files.
Funding: The authors received no specific funding
for this work.
Competing Interests: At the time of the analysis, AK
was employed by Celgene Corporation, with
ownership of stock in Celgene Corporation.
threshold of one time per capita GDP, suggesting that AV is highly cost-effective for the
treatment of snakebite in all 16 WA countries. The findings were consistent even with varia-
tions of inputs in 1way sensitivity analyses. In addition, the PSA showed that in the major-
ity of iterations ranging from 97.3% in Liberia to 100% in Cameroun, Guinea Bissau, Mali,
Nigeria and Senegal, our model results yielded an ICER that fell below the threshold of one
time per capita GDP, thus, indicating a high degree of confidence in our results.
Conclusions
Therapy for SBE with AV in countries of WA is highly cost-effective at commonly accepted
thresholds. Broadening access to effective AVs in rural communities in West Africa is a
priority.
Author Summary
Antivenom is the main intervention against snakebite poisoning but is relatively scarce,
unaffordable and the situation has been compounded further by the recent cessation of
production of effective antivenoms and marketing of inappropriate products. Given this
crisis, we assessed the cost effectiveness of providing antivenoms in West Africa by com-
paring costs associated with antivenom treatment against their health benefits in decreas-
ing mortality. In the most comprehensive analyses ever conducted, it was observed the
incremental cost effectiveness ratio of providing antivenom ranged from $1,997 in Guinea
Bissau to $6,205 for Liberia and Sierra-Leone per death averted while cost per Disability
Adjusted Life Year (DALY) averted ranged from $83 for Benin Republic to $281 for
Sierra-Leone. There is probability of 97.3100% that antivenoms are very cost-effective in
the analyses. These demonstrate antivenom is highly cost-effective and compares favor-
ably to other commonly funded healthcare interventions. Providing and broadening anti-
venom access throughout areas at risk in rural West Africa should be prioritized given the
considerable reduction in deaths and DALYs that could be derived at a relatively small
cost.
Introduction
Snakebite poisoning is a significant cause of death and disability in rural West Africa
[1,2,3,4,5,6,7]. The exact burden of snakebite is difficult to ascertain and is often undere-
ported. A study by Jean-Philippe Chippaux reported an estimate of over 314, 000 envenom-
ations, 7300 mortality and nearly 6000 amputations occurring yearly in sub-Saharan Africa
(SSA) [7]. However, even in West Africa alone, a range of 1504 to 18,654 annual mortality
from snakebite envenoming has been made [8]. This is further compounded by the variabil-
ity in snakebite incidence with estimates of as high as 500 bites per 100,000 persons per year
in parts of northern Nigeria [9].
Vipers (Echis ocellatus,E.leucogaster and E.jogeri) are a major cause of snakebite envenom-
ing throughout the sub-region mainly in Benin republic, Burkina Faso, Cameroun, Chad,
Gambia, Ghana, Mali, Niger, Nigeria, Togo and Senegal [1,2,3,4,5,6,7]. In the sub-region,
envenoming from snakes other than vipers mostly results from African spitting cobras (Naja
nigricollis,N.katiensis), puff-adder (Bitis arietans), mambas (Dendroaspis viridis,D.polylepis),
Cost-Effectiveness of Antivenoms for Snakebite in West Africa
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004568 March 30, 2016 2 / 16
burrowing asps or stiletto snakes (Atractaspis species), night adders (Causus maculatus,C.
rhombeatus,C.resimus,C.lichtensteinii) and very rarely boomslang (Dispholidus typus).
Jogers carpet viper (E.jogeri) is confined to Mali. Romanes carpet viper (Echis leucogaster)
and Egyptian cobras (Naja haje and N.senegalensis) are causes of snakebite envenoming in the
Sahelian and drier parts of West Africa while the forest cobra (Naja melanoleuca) and the Gab-
oon viper (Bitis gabonica) cause occasional bites in the rain forest and South-eastern parts of
the sub-region [1,5,7].
In West Africa, carpet vipers may account for as many as two thirds of all snakebite enven-
oming although their range is limited to the savannah region [1,9,10,11]. Envenoming from
carpet vipers leads to swelling and tissue damage at the site of bite, local and systematic bleed-
ing, anaemia and shock. Often death results from cerebral haemorrhage, bleeding elsewhere or
haemorrhagic shock [1,10,11]. The bleeding abnormality results from a prothrombin activating
metalloprotease Ecarinand a FX activating component, an anticoagulant, platelet activator/
inhibitor and haemorrhagins in the snakes venom [1,10,11]. Non-clotting blood detected by
the 20minute Whole Blood Clotting Test [20WBCT] virtually confirms carpet viper envenom-
ing in the northern third of Africa (roughly north of the equator) and is utilized to assess ade-
quacy of treatment [1,10,11]. Most non-carpet viper bites lead to local swelling and tissue
damage. The colubrids, boomslangs and twig snake (Thelotornis kirtlandii), are back fanged
snakes that rarely envenom but can cause severe bleeding and acute kidney injury. Neurotoxic
features may result from Naja haje,Naja melanoleuca and Dendroaspis spp bites with deaths
often resulting from respiratory muscle paralysis [12]. The risk of death from snakebites other
than viper envenoming is lower [9,13,14,15,16,17], but cobra spits may lead to blindness and
bites to cancerous ulcers, abortions, scarring, arthrodeses, contractures and psychological
impairment leading to permanent disability and productivity loss following hospitalization and
incapacitation [7,18,19,20,21]. Cessation of bleeding abnormalities and restoration of clotting
following administration of effective antivenom usually occurs promptly in carpet viper enven-
oming. Antivenom is efficacious in decreasing the likelihood of dying and is the main treat-
ment for snakebite envenoming [1,11,22,23]. However, its administration is associated with
early adverse reactions (EAR) which rarely results in fatality.[24,25,26]. Specific interventions
may be required to either prevent EAR with administration of premedication prior to anti-
venom or to treat it once developed following antivenom administration [25,26]. Antivenoms
are formulated as either liquid agents that needs to conveyed and stored at low temperature
with a life span of about three years [27,28] or as freeze dried substances that are more stable
with extended shelf life. Both types of formulations have been produced for the sub-region
[6,27,28]. The average cost per treatment of antivenom was reported as US$124 (range US$55
$640) although a median price of US$153 was also reported for Sub-Saharan Africa [29,30,31].
The few effective antivenoms in the sub-region generally have been scarce, locally unaffordable
and inaccessible where they are most needed. Partly for these reasons antivenom utilization
has drastically declined to a very small fraction of indicated need. The situation has been com-
pounded further by the recent announcement by Sanofi-Pasteur that production and distribu-
tion of FAV Afrique, currently the most widely distributed and most dependable antivenom in
the sub-region, will be discontinued by 2016. Its loss will exacerbate an already serious public
health crisis and makes the management of snakebite even more challenging [32]. It is there-
fore extremely important within the context of other competing public health priorities to
assess the health economics of antivenoms to guide policy. Before the recent publication of our
work focusing on Nigeria [33], few economic evaluations of preliminary nature had been con-
ducted on antivenoms [34,35]. Here, we evaluated the cost-effectiveness of antivenom utility in
the treatment of snakebite envenomation by computing incremental cost effectiveness ratios
(ICERs) of the cost per death averted and the cost per DALY averted by adapting a previously
Cost-Effectiveness of Antivenoms for Snakebite in West Africa
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004568 March 30, 2016 3 / 16
published model for Nigeria to 16 countries in WA. We performed the analysis from health-
care system perspective to provide policy makers with evidence towards broadening access to
antivenoms given their importance in preventing loss of lives and limbs among poor vulnerable
communities in West Africa.
Materials and Methods
Model Overview
A decision analytic model (Fig 1) was adapted to estimate health outcomes and costs associated
with the availability and use of geographically appropriate and effective antivenoms for snake-
bite poisoning in West Africa [33]. Details of the model structure are described elsewhere [33].
Briefly, the model assessed the availability of effective antivenoms relative to no availability in
the decision node. The model differentiated snakebite envenoming by carpet viper and non-
carpet viper and distinction was made on the basis of the 20WBCT in the treatment arm of the
model. Evidence of coagulopathy would lead to the administration of mono-specific antivenom
that neutralizes carpet viper venom only, whereas absence of coagulopathy triggers the admin-
istration of a polyspecific antivenom that neutralizes venoms from several snakes, including
the carpet viper. In the first chance node, the model included EARs associated with antivenom
use, which are more likely to occur with polyspecific rather than the monospecific antivenom
[23,27,28,36,37]. Symptoms of EAR were diverse and death could happen in about 1% of cases
[24,25,26]. Survivors of snakebite may recover completely or remain with significant sequaela
(e.g. amputation) that was considered in the model. Treatment outcomes were converted into
DALYs on the basis of local life expectancy. Tree Age Pro Suite Healthcare 2014 software was
used for analyses.
Model Inputs
Antivenom effectiveness and Early Adverse Reactions (EAR) data. The likelihood of
death from carpet viper and other snakebites among untreated victims was previously reported
at 8.115.83% and 527.3% respectively [9,10,38,39,40,41,42] although these were varied in
sensitivity analyses. When data on antivenom effectiveness was available for a given country,
it was applied for that country. It ranged from 56.43% to 92% against carpet viper deaths. A
meta-analysis estimate was applied for countries without data (Table 1)[38,39,40]. There
hasnt been placebo-controlled randomized controlled trials (RCT) ever conducted for anti-
venom assessment and the estimates of effectiveness derived from the meta-analysis that exclu-
sively only included observational studies from Chad, Ghana and Nigeria [10,22,37,38,39] were
applied in the model. Results from the meta-analysis suggested that an effective antivenom has
a 75% (95% confidence interval: 5586%) effectiveness in averting mortality from carpet viper
bites [22]. Since the meta-analysis included studies wherein polyspecific antivenoms were used,
these estimates of effectiveness were applied against non-carpet viper deaths except in Benin
and Guinea-Conakry, where country-level effectiveness data exists for Antivipmyn antivenom
against non-carpet viper (elapid) deaths, reported at 43.6% (080.5%) (Table 1)[42]. However,
in a scenario analysis antivenoms were assumed to be ineffective (0%) against non-carpet viper
envenoming. Estimates of EAR for the corresponding antivenoms were Antivipmyn 3.3% and
FAV Afrique 4.3% as obtained in observational studies while it was EchiTab-G 19% and Echi-
Tab-Plus 26% [23,36,37]. For countries where none of the antivenoms have been in use, the
EAR risk median estimate of 4.3% was used in the model [36]. The EAR estimates were varied
from 0% to 30% in sensitivity analyses. The risk for disability (limb amputation) among survi-
vors was approximated to 3% from studies in sub-Saharan Africa and the tropics [7,43,44]. In
base-case analysis antivenom administration had no effect on amputation, however,
Cost-Effectiveness of Antivenoms for Snakebite in West Africa
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004568 March 30, 2016 4 / 16
Fig 1. Decision tree model for managing snakebite envenoming with or without FAV Afrique antivenom in Cameroun (each of the 16 countries has
a similar model with its data input). Model parameter definitions: c20WBCTest = cost of 20 minutes Whole Blood Clotting Test on 10 occassions over 7
days at diagnoses and monitoring; cAdvReaction = Cost of managing early adverse reactions; cAntivenom = Cost of Antivenom; cFeed_Transp = Cost of
transporation and stay in Hospital for 7days; cRefrg_Transp = Cost of shipping and refrigeration; cNoAntivenom = Cost of management without effective
antivenoms either traditional/herbal care or other alternatives; cSupp_care = Cost of supportive care. All costs are in US$. antivenomeff = Effectiveness of
Cost-Effectiveness of Antivenoms for Snakebite in West Africa
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004568 March 30, 2016 5 / 16
effectiveness was applied in sensitivity analyses. The mean ages of snakebite envenomed vic-
tims were reported for Chad 25.2 years, Niger 29 years, Nigeria 26 years and Mali 28 years
[38,39,41,45,46]. So, since snakebite envenoming occurs among persons with average age in
the 2529 year age group, we determined the remaining local life expectancies in this age group
for the 16 countries ranged from 37 years in Sierra-Leone to 45 years in Ghana and Senegal
(Table 1)[47]. The base-case analysis on disability was restricted to extremity amputation
although blindness from venom-ophthalmia and Post Traumatic Stress Disorder (PTSD)
from encountering snake with respective disability weights of 0.552 and 0.105 [48] were also
explored in scenario analyses. An annual discount rate of 3% was applied on the health out-
comes (mortality and amputation) and the associated amputation-related disability weight
used was 0.102 [48]. The model was adapted to 3 types of antivenoms used in WA: Antivipmyn
in Benin and Guinea Conakry; EchiTab-G and EchiTab-Plus in Burkina Faso and Nigeria;
FAV Afrique in Cameroun, Chad, Ghana and Mali. For the remaining 8 countries without evi-
dence of effectiveness data for a particular antivenom, the meta-analytic estimates were used
[22]. Where other required data item was unavailable, data from adjacent or neighboring coun-
tries were used to input a model with mixed data sources. These parameters for the respective
models were obtained in the literature and imputed to the antivenom-defined models and was
run for each of the 16 countries.
Cost data. The cost of the full antivenom treatment regimen was modeled as US$153
[29,30,31]. The cost of care, ten 20WBCT measurements in 7 days, transportation to-and-from
hospital and feeding for 7 days, shipping and freezing of antivenom, management of EAR, sup-
portive care (such as pain relief, blood transfusion, medications, fluid replacement and wound
management) were obtained from series of envenomed patients admitted to Kaltungo General
Hospital in Nigeria Table 2 [33]. All costs were expressed in US$. Given snakebite is a short
term condition and costs occur during a brief period of time (2 to 10 days), costs were not dis-
counted to adjust for time elapsed between expenditure and outcome during Incremental Cost
Effectiveness Ratio (ICER) calculations [49,50]. As a conservative analysis the alternative of no
antivenom therapy carried a cost of zero as no treatment, care, test and EAR management was
provided. However, in a scenario analysis cost of $65.63 was added/incurred for the alternative
of no antivenom therapy, comprising of supportive care $18.75, feeding and transportation
$43.75, and for 20WBCT $3.125. The ICER was computed by dividing total cost by the differ-
ence in DALYs (e.g., cost/DALY averted) [49,50].
Sensitivity analysis. One-way sensitivity analysis was performed for select input variables
to test robustness and determine the most important variables influencing cost-effectiveness
of an antivenom programme. Each base-case model input was varied independently according
to the upper and lower limits obtained from literature and according to low and high value
scenarios.
In addition, Probablistic Sensitivity Analyses (PSA) were performed using Monte Carlo sim-
ulation by running 10,000 iterations of the model while randomly selecting the values for 16
key model inputs from a probability distribution that was defined for each of the parameters
(Table 2). This process enabled us to estimate the 95% confidence interval around the base case
ICER estimates for each of the 16 countries included in the analysis, and it also allowed us to
estimate the probability that antivenom therapy is cost-effective by calculating the proportion
antivenom to prevent death; pEARmono = probability of early adverse reactionswith monospecific antivenom; pEARpoly = probability of early adverse
reactionswith polyspecific antivenom; pEARmort = probability of dying following effective antivenom andearly adverse reactions; pCVmort = probability of
dying following carpet viper envenoming; pNCVmort = probability of dying following non-carpet viper envenoming; pCV = proportion of envenoming due to
carpet viper; pDisabl = probability of disability; dw = disability weighting of consequences of snakebite envenoming; x = effect of adrenaline premedication
reduction of risk of early adverse reactions.
doi:10.1371/journal.pntd.0004568.g001
Cost-Effectiveness of Antivenoms for Snakebite in West Africa
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004568 March 30, 2016 6 / 16
Table 1. Data estimates used in the model by country.
(a) Mean age at
bite
(+remaining
life expectancy
[2012]), years
(b) Proportion
of envenoming
due to CV or
vipers (%)
(c)
Untreated
Mortality
(CV; Non-
CV)
(d)
Mortality
post AV
(CV; Non-
CV)
AV effectiveness
against mortality
(e) = [1-RR] or
alternatively = (c-
d)/c (for CV; Non-
CV)
Risk of Early
Adverse
Reactions
with CV
(mono) and
NCV(poly[(%)
Comments References
Model 1: Antivipmyn Antivenom
Benin
Republic
2529 (44) 85% 15%; 9/33
(27.3%)
3.11%; 4/
26(15.4%)
79.3%; (NA)
43.6% (080.5%)
3.3% Used NCV
data from
Guinea
Fayomi et al 2002
[4]; Chippaux et al
2007 [6]; Balde
et al 2012 [37];
Balde et al 2013
[42];
Guinea-
Conakry
2529 (43) 83% 15%; 9/33
(27.3%)
3.11%; 4/
26(15.4%)
79.3%; (NA)
43.6% (080.5%)
3.3% Used CV
data from
Benin
Fayomi et al 2002
[4]; Chippaux et al
2007 [6]; Balde
et al 2012 [37];
Balde et al 2013
[42]; Adehossi
et al 2011 [45];
Model 2: EchiTab-G and EchiTab-Plus Antivenom
Nigeria 26 (41) 66% 19/120
(15.83%);
5%
78/6137
(1.27%)
92% (8795%) ET-19%;
ETPlus-26%
Warrell et al 1977
[10]; Abubakar
et al 2010[23];
Habib &
Abubakar 2011
[38]; Pugh et al
1980 [13]
Burkina
Faso
2529 (43) 85% 12.1%; 5% NA 92% (8795%) ET-19%;
ETPlus-26%
Used AV
effect from
Nigeria;
Ghana
mortality
Warrell et al 1977
[10]; Abubakar
et al 2010[23];
Habib &
Abubakar 2011
[38]; Visser et al
2008 [40]; Pugh
et al 1980 [13]
Model 3: FAV Afrique Antivenom
Cameroon 2529 (41) 85% 15/98
(15.3%)
NA 85.2%(56.195%); 4.3% Used (c) &
(e) from
Chad/Ghana
Chippaux et al
1999 [36];
Bregani et al
2006 [39]; Visser
et al 2008 [40];
Chad 25.2 (38) 85% 15/98
(15.3%)
4/60
(6.67%)
56.43% (085.2%); 4.3% Chippaux et al
1999 [36];
Bregani et al
2006 [39];
Ghana 2529 (45) 85% 8/66
(12.1%); -
5/278
(1.8%)
85.2%(56.195%); 4.3% Chippaux et al
1999 [36]; Visser
et al 2008 [40];
Mali 28 (43) 85% 8.1%; 5% 1.5% 81.48% (NA) 4.3% Chippaux et al
1999 [36]; Drame
et al 2012 [41]
Other/Multiple Antivenoms
Cote
dIvoire
2529 (39) 83% 12.1%;- 75%(5586%)- 4.3% AV efcacy
from meta-
analysis
Habib & Warrell
2013 [22];
Chippaux et al
1999 [36]; Visser
et al 2008 [40];
(Continued)
Cost-Effectiveness of Antivenoms for Snakebite in West Africa
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004568 March 30, 2016 7 / 16
of 10,000 iterations that resulted in ICERs that fell below commonly accepted cost-effectiveness
thresholds of one time per capita Gross Domestic Product (GDP) for each of the 16 countries
[51,52].
The study reporting was done consistent to standard guidelines for cost effectiveness analy-
ses and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) state-
ment [49,50,52,53,54].
Results
The cost/death averted for the 16 countries of interest varied. It was as low as $1,997 in Guinea
Bissau to as high as $6,205 in Liberia and Sierra Leone. The cost/DALY averted ranged from a
low of $83 (95% Confidence Interval: $36-$240) for Benin Republic to a high of $281 ($159
457) for Sierra-Leone. In all cases, the base-case cost/DALY averted estimate fell below the
Table 1. (Continued)
(a) Mean age at
bite
(+remaining
life expectancy
[2012]), years
(b) Proportion
of envenoming
due to CV or
vipers (%)
(c)
Untreated
Mortality
(CV; Non-
CV)
(d)
Mortality
post AV
(CV; Non-
CV)
AV effectiveness
against mortality
(e) = [1-RR] or
alternatively = (c-
d)/c (for CV; Non-
CV)
Risk of Early
Adverse
Reactions
with CV
(mono) and
NCV(poly[(%)
Comments References
Gambia 2529 (44) 40% 14.3% 75%(5586%) 4.3% Enwere et al 2000
[3]; Habib &
Warrell 2013 [22];
Chippaux et al
1999 [36];
Guinea-
Bissau
2529 (41) 40% 15%; 27.3% 75%(5586%);
43.6% (080.5%)
4.3% Habib & Warrell
2013 [22]; Balde
et al 2013 [42];
Adehossi et al
2011 [45];
Liberia 2529 (44) 0% (*1%) 0%
(*15%);5%
75%(5586%) 4.3% Pugh et al 1980
[13] Habib &
Warrell 2013 [22];
Niger 29 (44) 85% 15%; 5% 75%(5586%) 4.3% Habib & Warrell
2013 [22];
Chippaux et al
1999 [36]; Fayomi
et al 2002 [4];
Adehossi et al
2011 [45];
Senegal 2529 (45) 40% 15%;5% 75%(5586%) 4.3% Trape et al 2002
[5];Habib &
Warrell 2013 [22];
Chippaux et al
1999 [36];
Adehossi et al
2011 [45];
Sierra-
Leone
2529 (37) 0% (*1%) 0%
(*15%);5%
75%(5586%) 4.3% Pugh et al 1980
[13] Habib &
Warrell 2013 [22];
Togo 2529 (43) 85% 12.1%; 5% 75%(5586%)4.3% Habib & Warrell
2013 [22]; Visser
et al 2008 [40];
CVcarpet viper; RRRelative Risk
doi:10.1371/journal.pntd.0004568.t001
Cost-Effectiveness of Antivenoms for Snakebite in West Africa
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004568 March 30, 2016 8 / 16
commonly accepted threshold of one time per capita GDP, suggesting that AV is highly cost-
effective for the treatment of snakebite in all 16 WA countries [51,52].
The findings from the analyses were also consistent to variations of inputs in 1-way sensitiv-
ity and scenario analyses as depicted (Table 3 and Fig 2). The individual countriesmodel
results were most sensitive to effectiveness of antivenom in decreasing mortality, natural (unat-
tended) mortality, costs of antivenoms and types of snake causing envenoming (Fig 2). Results
were not sensitive to antivenom associated EAR or the cost of managing it. Varying the cost
of antivenom from $125 to two times for victims who may require two doses, i.e. $306, still
yielded ICER estimates that remain cost-effective. The ICERs rose when the frequency of
snakebite envenomation due to saw-scaled viper was reduced to 0% except in Benin and
Guinea Conakry where Antivipmyn antivenom is used and is effective even against elapids
(Table 3)[42].
Moreover, the ICER ranged from $97.26 in Benin to high levels of $13,964.26 in Liberia and
$15,278.99 in Sierra Leone even in the worst case scenario where (poly-specific) antivenoms
have nil effectiveness (0%) against bites from snakes other than carpet viper. These estimates
fall outside the cost-effectiveness thresholds in Liberia and Sierra Leone largely because non-
carpet viper accounts for 99% of SBE. Applying a modest reduction of 40% on the probability
of EAR with the use of adrenaline premedication [25,26,33] gave a cost per DALY averted
slightly lower than base-case ICERs. Similarly, the ICERs were only very slightly altered even
when more serious or more frequent disabilities were substituted in the model. This was dem-
onstrated with venom-induced-blindness (0.01%) or Post-Traumatic-Stress-Disorder (20%)
with disability-weights of 0.552 and 0.105 respectively [18,21,48].
Furthermore, our PSA confirms the model findings remain consistent to concurrent varia-
tion of all model inputs, as the ICERs with their respective 95% confidence limits are far less
than the cost-effectiveness thresholds (Table 3). It showed that in majority of simulations
(97.3% in Liberia to 100% in Cameroun, Guinea Bissau, Mali, Nigeria and Senegal (Fig 3)) our
Table 2. General assumptions used in Monte Carlo simulations.
Assumption Base Case Value (BCV) Range of BCVs Distribution Reference
Proportion of envenoming due to CV/ Non-Elapids (%) Varies by country 185% Beta 1,5,6,7,36
Mortality due to untreated CV envenoming (%) Varies by country 8.115.83% Beta 3,4,10,39,40,41,45
Mortality due to untreated Non-CV/Elapid envenoming (%) Varies by country 527.3% Beta 13,14,42
AV effectiveness against CV mortality (%) Varies by country 56.4392% Beta 4,6,10,22,38,39,40,41
AV effectiveness against Non-CV/Elapid mortality (%) Varies by country 43.692% Beta 10,38,42
Risk of AV EAR for CV envenoming (%) Varies by country 3.319% Beta 23,36,37
Risk of AV EAR for Non-CV envenoming (%) Varies by country 3.326% Beta 23,36,37
Risk of AV EAR mortality (%) 1% Same for each country Beta 24
Risk of amputation following envenoming (%) 3% Same for each country Beta 7,43,44
Disability weight for amputation 0.102 Same for each country Beta 48
Cost of antivenom (US$) $153 Same for each country Normal 29,30,31
Cost of 20min Whole Blood Clotting Test $3.125 Same for each country Normal 33
Cost of managing Early Adverse Reactions $1.875 Same for each country Normal 33
Cost of supportive care $18.75 Same for each country Normal 33
Cost of feeding and transportation $43.75 Same for each country Normal 33
Cost of refrigeration and transportation $18.75 Same for each country Normal 33
Cost of no antivenom (US$) $0 Same for each country Not varied Our assumption
DALYs averted per death averted (3% discounted) Varies by country 22.1724.52 Not varied Our calculations
DALYs averted per amputation averted (3% discounted) Varies by country 2.262.50 Not varied Our calculations
doi:10.1371/journal.pntd.0004568.t002
Cost-Effectiveness of Antivenoms for Snakebite in West Africa
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004568 March 30, 2016 9 / 16
Table 3. Results from model outputs by country and scenarios.
Country and
GDP/Capita
($) [49]
Increm Cost
Effect Ratio
[ICER]/DALY
($) (95%
Conf.
Interval)
Cost/
Death
Averted
($)
Probability
Antivenom is
cost-effective
(%)
ICER if
Antivenom
Cost = $125
ICER if
Antivenom
Cost = $306
ICER if
proportion of
Carpet
Viper = 0% ($)
ICER if Av
Effect for Non
Carpet
Viper = 0% ($)
ICER if the No
Antivenomarm
paid for Basic
costs of $65.63*
Benin (751) 82.63 (36.41
240.09)
1997.91 99.99 72.87 135.96 81.75 97.26 59.75
B/Faso (652) 99.44 (40.39
377.40)
2384.81 99.61 87.98 164.05 226.53 107.18 71.94
Cameroun
(1220)
86.97 (38.47
240.43)
2030.05 100.00 76.70 143.11 238.39 92.01 62.89
Chad (1035) 136.94
(51.33
704.75)
3070.80 99.13 120.77 225.34 376.61 144.89 99.03
Cote dIvoire
(1366)
128.24
(51.20
461.64)
2916.02 99.97 113.09 211.04 278.37 139.16 92.73
Gambia
(509)
150.08
(72.18
305.49)
3628.88 99.99 132.25 247.47 261.77 229.59 108.30
Ghana
(1646)
103.61
(42.04
372.87)
2532.73 99.99 91.38 170.50 227.63 111.21 74.93
Guinea
Bissau (576)
87.09 (44.96
171.55)
2032.72 100.00 76.75 143.60 84.76 226.64 62.85
Guinea
Conakry
(493)
83.54 (36.59
236.35)
1997.41 99.98 73.67 137.49 82.68 100.72 60.40
Liberia (414) 256.61
(147.67
417.68)
6204.95 97.28 226.00 423.92 261.77 13,964.26 184.85
Mali (696) 160.48
(82.21
306.83)
3836.74 100.00 141.52 264.06 243.47 178.09 116.04
Niger (385) 97.23 (39.84
328.02)
2351.06 98.64 85.75 159.99 261.77 102.98 70.31
Nigeria
(2742)
92.56 (40.27
242.63)
2160.33 100.00 81.61 152.35 232.04 107.96 66.91
Senegal
(1023)
143.81
(67.34
317.76)
3515.25 100.00 126.73 237.14 258.95 216.41 103.78
Sierra Leone
(590)
280.77
(158.51
456.68)
6204.95 99.86 247.27 463.83 286.42 15,278.99 202.25
Togo (589) 120.42
(47.62
455.04)
2878.98 98.86 106.19 198.14 264.75 129.25 87.08
*Scenario of Basic costs in the No antivenom arm = Cost of supportive care ($18.75) + Cost of feeding and transportation ($43.75) + Cost of 20min Whole
Blood Clotting Test ($3.125) = $65.63
AVantivenom; ICERIncremental Cost Effectiveness Ratio;
doi:10.1371/journal.pntd.0004568.t003
Cost-Effectiveness of Antivenoms for Snakebite in West Africa
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004568 March 30, 2016 10 / 16
model results yielded an ICER that fell below the threshold of one time per capita GDP, thus,
indicating a high degree of confidence in our results [51,52].
Discussion
Economic modeling is very useful in determining the best ways to utilize resources to optimally
manage medical conditions where there are competing priorities and limited resources [49].
This is the first extensive assessment of the cost-effectiveness of expanding antivenom access in
the 16 countries in West Africa. We find that the cost/death averted for the 16 countries of
interest ranged from $1,997 in Guinea Bissau to $6,205 for Liberia and Sierra Leone. The cost/
DALY averted ranged from $83 (95% Confidence Interval: $36-$240) for Benin Republic to
$281 ($159457) for Sierra-Leone. The ICER point estimate is <$100/DALY averted in 7 coun-
tries, $100-$200/DALY averted in 7 countries and <$300/DALY averted in 2 countries. The
results show that snakebite antivenoms are highly cost-effective in West Africa, as our findings
are far less than the one time per capita GDP threshold [51,52]. While it will be worthwhile to
repeat the analysis for similar geographic and socioeconomic settings, most of the model inputs
such as the antivenom efficacy and cost would largely be similar across many African countries
Fig 2. Tornado diagrams assessing the impact of changes in envenoming/antivenom and cost parameters on the incremental cost-effectiveness
ratio (ICER) per DALY for antivenom use in Guinea Bissau (L) and Senegal (R). Diagram parameter definitions: c20WBCTest = cost of 20 minutes
Whole Blood Clotting Test on 10 occassions over 7 days at diagnoses and monitoring; cAntivenom = Cost of Antivenom; cFeed_Transp = Cost of
transporation and stay in Hospital for 7days; cRefrg_Transp = Cost of shipping and refrigeration; cNoAntivenom = Cost of management without effective
antivenoms either traditional/herbal care or other alternatives; cSupp_care = Cost of supportive care. All costs are in US$. Antivenomeff = Effectiveness of
antivenom to prevent death; pEARmono = probability of early adverse reactions with monospecific antivenom; pEARpoly = probability of early adverse
reactionswith polyspecific antivenom; pEARmort = probability of dying following effective antivenom andearly adverse reactions; pCVmort = probability of
dying following carpet viper envenoming; pNCVmort = probability of dying following non-carpet viper envenoming; pCV = proportion of envenoming due to
carpet viper; pDisabl = probability of disability.
doi:10.1371/journal.pntd.0004568.g002
Cost-Effectiveness of Antivenoms for Snakebite in West Africa
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004568 March 30, 2016 11 / 16
with similar GDPs where snakebite envenoming occurs. An exception may be the prevalence
of carpet viper (Echis ocellatus) envenoming, a snake that is confined to West Africa extending
eastwards only as far as Chad and Central Africa Republic. However, even in areas without car-
pet viper bites (0%) our results demonstrate that antivenoms remain highly cost-effective.
The combination of effective and relatively inexpensive antivenoms and the utilization of a
cheap, dependable and simple point-of-care test have been instrumental to our results. Anti-
venom effectiveness is loosely inversely related to the ICER per DALY saved (Fig 2)[33]. With
discontinuation of production of geographically appropriate effective antivenoms and market-
ing of inappropriate ineffective products the cost per DALY saved will substantially soar
[32,39,40]. The 20WBCT is discriminatory and will be useful following envenoming from
other snakes in the rest of Africa that result in coagulopathy e.g., other species of carpet viper
(Echis leucogaster,Echis pyramidum,Echis jogeri,Echis coloratus) and boomslang. In the
Fig 3. Monte Carlo Simulation showing the probability antivenom is cost-effective in majority of iterations (out of 10,000) for 4 countries with
respective Willingness To Pay (GDP/capita) and probabilities: top panel Chad (WTP $1035; prob-99.13%) [L] and Liberia (WTP $414; prob-97.28%)
[R] and bottom panel Niger (WTP $385; prob-98.64%) [L] and Togo (WTP $589; prob-98.86%) [R].
doi:10.1371/journal.pntd.0004568.g003
Cost-Effectiveness of Antivenoms for Snakebite in West Africa
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004568 March 30, 2016 12 / 16
context of differing circumstances where multiple types of snakes with varying manifestations
of envenoming or lack of reliable cheap differentiating test, antivenoms may not be as cost-
effective. Nevertheless, where patients come along with the dead snakes, decision on antivenom
choice is feasible [23] and in such cases the differentiating test becomes not so useful. In the
face of competing health needs and constrained-resources, it would be helpful to contextualize
our findings in the light of other healthcare initiatives. The cost-effectiveness of Human Immu-
nodeficiency Virus treatment used in similar resource-constrained settings as first-line, sec-
ond-line or for protecting negative partners among discordant partners ranged from US$530
to US$1037 per year of life gained [33,55,56,57]. However, these estimates are still higher than
the highest ICERs obtained for two countries in this analysis, i.e., Liberia and Sierra-Leone
with $257/DALY averted and $281/DALY averted respectively. The antivenom cost effective-
ness is comparable to what obtains in other healthcare programmes. For example, the cost/
DALY averted obtained in this study ranged from $100 to $200 for 7 countries (see Table 3)
and is comparable to the cost effectiveness of rotavirus vaccines in other developing countries
in Africa and Asia [33,58,59]. Similarly, the cost/DALY averted in the remaining 7 countries
was <$100/DALY averted and is similar to what obtains for preventing Human Papilloma
Virus and pneumococcal infections with vaccines in West Africa [33,60,61].
We estimated a cost/DALY averted ranging from $73 in Benin to $247 in Sierra Leone if the
cost input of antivenom is reduced to $125 per dose as obtained in Mali [30]. Doubling the cost
of antivenom for patients requiring more than a dose still yielded ICERs that remain cost effec-
tive ranging from $136/DALY averted in Benin to $464/DALY averted in Sierra Leone.
In 8 of the 16 countries with neither indigenous antivenom effectiveness data nor data from
adjacent countries, we used efficacy derived from a meta-analysis with data inputs from other
countries in the sub-region [22,38].
The study has a number of limitations. First, the effectiveness of antivenom was derived
from observational studies rather than RCTs. Definitive placebo controlled trials of anti-
venom are considered unethical and RCTs are unlikely to be conducted in the absence of a
suitable comparator to antivenom. However, to reduce bias, improve data quality and validity
of estimates, three investigators independently searched both English and French literature
and extracted data using a checklist for consistency. Secondly, we applied the estimated pro-
tection conferred by antivenoms against carpet viper envenoming to the antivenoms used for
other than carpet viper envenoming (except in Benin and Guinea Conakry with specific esti-
mates), though this assumption was subsequently dropped in a scenario analysis where anti-
venoms were assumed to be ineffective (0%) against non-carpet viper envenoming. Thirdly,
the analysis mainly considered amputation as the major disability to the exclusion of other
anecdotal complications [7,20,43,44]. Fourthly, in our model, antivenoms only conferred
protection against deathbeing a more objective and valid outcome. Fifthly, other benefits
of antivenom (e.g. speedier recovery) were not included in the model. Sixth, we used separate
EAR risk inputs for EchiTab-G and EchiTab-Plus respectively [23] but could not discern
their respective efficacy against mortality so the combined estimate of the two was used in
Burkina Faso and Nigeria. Lastly, we did not include the costs incurred for logistics in con-
veying and preserving antivenoms as we assumed facilities for existing health programmes
will be utilized.
Conclusion
The findings from the cost effectiveness analysis demonstrate that providing and broadening
antivenom access throughout areas at risk in rural West Africa should be prioritized given the
considerable reduction in deaths and disabilities that could be derived at a relatively small cost.
Cost-Effectiveness of Antivenoms for Snakebite in West Africa
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004568 March 30, 2016 13 / 16
Author Contributions
Conceived and designed the experiments: AGH AK ML MAI MBM MH DAW JPC. Performed
the experiments: AGH AK ML. Analyzed the data: AGH AK ML MAI MBM MH DAW JPC.
Contributed reagents/materials/analysis tools: AGH AK ML. Wrote the paper: AGH AK ML
MAI MBM MH DAW JPC.
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Cost-Effectiveness of Antivenoms for Snakebite in West Africa
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004568 March 30, 2016 16 / 16
... Specifically, the Echisocellantus is by far the most common cause of morbidity and mortality in North-Eastern Nigeria [6]. Nigeria is known to be home to a lot of diverse snake species especially in the North Eastern part of the Savannah region with 100-150 lethality in hospitals and also overall mortality of 15.6 daily in Kaltungo [7]. Snake bite envenomation survivors live with temporary or permanent disabilities such as amputation, blindness, disfigurement, mutilation and psychological consequence from depression. ...
... The anti-snake venom in this hospital is totally free this could be the reason behind the increased influx of snakebite victims to the Hospital. This correlates with several studies in this region that reported an average lethality of 100-150 in hospitals and an overall mortality of 15.6 daily in Kaltungo [7,[18][19][20]. ...
... The most medically important snake species in those areas are Echis ocellantus (Carpet viper), Bitis arientans (Puff adder) and Naja nigrocolis (Black spitting copra). This has been documented in a lot of literatures [4,7,19,24,25]. ...
Chapter
Full-text available
Snake envenomation is increasingly recognized as a serious, worldwide public health concern and a neglected tropical disease of global importance especially in the North Eastern Nigeria. The scarcity of data regarding such snake fauna couple with its ability to inflict immense misery to the poorest of the population justifies the need to identify such snakes and some of the clinical features of snakebite victims in these endemic areas. Both primary and secondary data were collected during the study. Result revealed that 10 venomous snake species were reported in Gombe, Taraba and Bauchi state. The most abundant snake species is the Echis ocel�lantus (Carpet or saw scaled viper) having the highest frequency of encounter fol�lowed by the Bitis arientans (Puff Adder) and Naja nigricolis (Black Spiting Cobra). The Kaltungo General Hospital in Gombe is one of the major treatment centers in the North-Eastern Nigeria. About 2945 Human snakebite cases were reported in the Hospital in the year 2018, the highest snake envenoming were observed in October with 16.1% frequency while January has the least snakebite cases of 1.7%. The burden of snakebite envenoming in the North-Eastern Nigeria is a serious public health challenge which desperately need to be addressed.
... The incidence of snakebites varied from 0.00 to 13 20.00], respectively). ...
... Burkina Faso is the only sub-Saharan country where government subsidies allow for patients to receive a dose of antivenom (African Internal Standard Snake Antivenom Serum) at only 5% of the original price (<3US$). 4,20 However, despite its low cost, antivenom is still not available in Burkina Faso health centers, with very few snakebite victims receiving antivenom immunotherapy. This is likely due to the continued use of traditional medicines and difficulties in distributing antivenom to rural health centers. ...
... Although our snake picture sample size is insufficient, several authors have previously shown that vipers, notably Echis ocellatus, are a major contributor to snakebite envenomation in West Africa and particularly in Burkina Faso. 5,8,18,20,23,24 We further encourage the National Program for the Control of Neglected Tropical Diseases to inform rural populations about the importance of bringing the killed culprit snake to the primary health center, as this will inform ophidian envenomation victim care. ...
Article
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Background Snakebite envenomation is a significant public health problem in Burkina Faso. Our study describes the epidemiological and therapeutic aspects of snakebite cases at primary health centers in Houet Province, which is located in the western area of Burkina Faso. Methods We conducted a retrospective study of 664 snakebite cases occurring at 10 primary health centers in Houet Province from January 2014 to December 2018. Data were collected from the patient consultation recording database registry system. Results Affected individuals had a male/female ratio of 1.31. The lowest annual incidences (0.02 [95% CI –0.01 to 0.05] and 0.24 [95% CI 0.05 to 0.43]) were observed in the urban primary health centers of Bolomakoté and Sarfalao, respectively. Rural primary health centers in Nasso in 2016 and in Soumousso in 2014 had the highest annual incidence (13.80 [95% CI 7.59 to 20.00] and 3.92 [95% CI 2.99 to 4.86], respectively). Of the 664 registered snakebite victims, none received antivenom immunotherapy treatment. Conclusion Our study shows that snakebite envenomation incidents are common at the 10 primary health centers in Houet Province. Furthermore, despite the lack of antivenom and often inadequate treatment at these primary health centers, they remain the first point of care for snakebite victims.
... Following Habib, et al., [49] and Hamza et al., [50], 23.41 discounted DALYs approximation is equivalent to one early mortality due to snakebite. Therefore, the deaths averted by each strategy shown in Table 9, column 2, were converted to DALYs by taking the product of the total number of deaths averted by each strategy and 23.41 DALYs and the results are shown in Table 11 column 2. Consequently, we computed the ICER in terms of DALY averted as health benefit yielding a cost/DALY averted of $95.88 for strategy B which is similar to the earlier findings in [49] and [50] (see Table 11). ...
... Following Habib, et al., [49] and Hamza et al., [50], 23.41 discounted DALYs approximation is equivalent to one early mortality due to snakebite. Therefore, the deaths averted by each strategy shown in Table 9, column 2, were converted to DALYs by taking the product of the total number of deaths averted by each strategy and 23.41 DALYs and the results are shown in Table 11 column 2. Consequently, we computed the ICER in terms of DALY averted as health benefit yielding a cost/DALY averted of $95.88 for strategy B which is similar to the earlier findings in [49] and [50] (see Table 11). However, the cost/DALY averted for strategy B is still higher than that of strategy A, thus, the former is eliminated from the list. ...
Article
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A mathematical model is designed to assess the impact of some interventional strategies for curtailing the burden of snakebite envenoming in a community. The model is fitted with real data set. Numerical simulations have shown that public health awareness of the susceptible individuals on snakebite preventive measures could reduce the number of envenoming and prevent deaths and disabilities in the population. The simulations further revealed that if at least fifty percent of snakebite envenoming patients receive early treatment with antivenom a substantial number of deaths will be averted. Furthermore, it is shown using optimal control that combining public health awareness and antivenom treatment averts the highest number of snakebite induced deaths and disability adjusted life years in the study area. To choose the best strategy amidst limited resources in the study area, cost effectiveness analysis in terms of incremental cost effectiveness ratio is performed. It has been established that the control efforts of combining public health awareness of the susceptible individuals and antivenom treatment for victims of snakebite envenoming is the most cost effective strategy. Approximately the sum of US$72,548 is needed to avert 117 deaths or 2,739 disability adjusted life years that are recorded within 21 months in the study area. Thus, the combination of these two control strategies is recommended.
... A decision analytic model was developed to simulate the course of snakebite victims in ASEAN which was adapted from previous economic evaluations of antivenoms for snakebite antivenom in West Africa (Fig 1) [13,14]. Victims who were bitten by snake sought for treatment either at conventional treatment (hospitals or healthcare facilities) or traditional treatment through traditional healers to reflect the treatment seeking behavior of victims in the region [5]. ...
Article
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Background Understanding the burden of snakebite is crucial for developing evidence-informed strate- gies to pursue the goal set by the World Health Organization to halve morbidity and mortality of snakebite by 2030. However, there was no such information in the Association of South- east Asian Nations (ASEAN) countries. Methodology A decision analytic model was developed to estimate annual burden of snakebite in seven countries, including Malaysia, Thailand, Indonesia, Philippines, Vietnam, Lao PDR, and Myanmar. Country-specific input parameters were sought from published literature, coun- try’s Ministry of Health, local data, and expert opinion. Economic burden was estimated from the societal perspective. Costs were expressed in 2019 US Dollars (USD). Disease burden was estimated as disability-adjusted life years (DALYs). Probabilistic sensitivity analysis was performed to estimate a 95% credible interval (CrI). Principal findings We estimated that annually there were 242,648 snakebite victims (95%CrI 209,810– 291,023) of which 15,909 (95%CrI 7,592–33,949) were dead and 954 (95%CrI 383–1,797) were amputated. We estimated that 161,835 snakebite victims (69% of victims who were indicated for antivenom treatment) were not treated with antivenom. Annual disease burden of snakebite was estimated at 391,979 DALYs (95%CrI 187,261–836,559 DALYs) with total costs of 2.5 billion USD (95%CrI 1.2–5.4 billion USD) that were equivalent to 0.09% (95% CrI 0.04–0.20%) of the region’s gross domestic product. >95% of the estimated burdens were attributed to premature deaths. Conclusion/Significance The estimated high burden of snakebite in ASEAN was demonstrated despite the availability of domestically produced antivenoms. Most burdens were attributed to premature deaths from snakebite envenoming which suggested that the remarkably high burden of snakebite could be averted. We emphasized the importance of funding research to perform a compre- hensive data collection on epidemiological and economic burden of snakebite to eventually reveal the true burden of snakebite in ASEAN and inform development of strategies to tackle the problem of snakebite.
... Given that a significant proportion of patients in rural areas in West Africa live below poverty threshold, the cost of ASVs and associated cost of care is often unfordable to these patients. [39][40][41] The chaotic drug supply chain is another important challenge in West Africa. As a result, ASVs are often out of stock in many health facilities and pharmacies. ...
Article
Snakebite envenomation (SBE) is an important public health issue that is now receiving renewed attention following its reclassification as a Neglected Tropical Disease (NTD). Most incidences occur in rural areas of resource‐limited countries, as such, timely and appropriate medical care for SBE is often inaccessible. The administration of anti‐snake venom serum (ASV) is the only effective definitive treatment of SBE, but treatment failure to available ASVs is not uncommon. Emerging evidence highlights the potential of small‐molecule compounds as inhibitors against toxins of snake venom. This presents an encouraging prospect to develop an alternative therapeutic option for the treatment SBE, that may be amenable for use at the point of care in resource‐constraint settings. In view of the pivotal role of natural products in modern drug discovery programmes, there is considerable interest in ethno‐pharmacological mining of medicinal plants and plant‐derived medicinal compounds towards developing novel snake venom‐neutralising therapeutics. In this review, we compile a collection of medicinal plants used in the treatment of SBE in West Africa and highlight their promise as potential botanical drugs or as sources of novel small molecule compounds for the treatment of SBE. The challenges that must be surmounted to bring this to fruition including the need for (sub) regional collaboration have been discussed.
... The available estimates cover health system costs and out-of-pocket expenditure of snakebite (Hasan et al., 2012), and the burden of snakebite (Habib et al., 2015). The cost per death averted has been estimated for 16 countries in West Africa (Hamza et al., 2016). Using data on mortality and amputations, the total burden of snakebite in West Africa has been estimated at 320,000 DALYs (95% CI: 248,000-403,000 DALYs) per year with Nigeria accounting for 43% of the burden (Habib et al., 2015). ...
Article
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The burden of disability among survivors and the socio-economic impact of snakebite have not been adequately researched. We reviewed original research articles, case reports and small case series relating to chronic physical, mental and psycho-social disability and economic burden of snakebite. Both physical and psychological health problems seem common in snakebite survivors and can lead to disability and loss of productivity. Chronic physical health effects, musculoskeletal disability being the commonest, can be largely attributed to limited and delayed access to optimal treatment of acute envenoming. The economic burden is considerable, and includes health system costs, out-of-pocket expenditure and opportunity costs, with regional variations. Health systems should be more responsive to needs and circumstances of bite victims, and a more holistic approach should be developed in the treatment of snakebite which incorporates the management of chronic health effects.
Book
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Snakes play a very important role in our ecosystem. They help in balancing the food web, regulating the population of their prey, and thereby controlling pests. They also exhibit both predator and prey characteristics and help in maintaining biodiversity on Earth for future sustainable development. This book highlights the extreme ecological importance of snakes with chapters on snake venom and its therapeutic potential and the ecology of some selected snake species.
Article
Cobra is a common snake throughout Africa and Asia, however, there are few literatures reporting neurotoxic cobra bite from Sub-Saharan Africa (SSA), including Northern Nigeria. Here, we report 3 cases that were bitten by cobra in the savannah region of Nigeria. All the 3 cases presented with features of severe neurotoxic envenomation: generalized hypotonia, ptosis, and features of autonomic dysfunction, which include excessive salivation and sweating. One of the 3 victims progressed to develop respiratory paralysis that resulted in death. The other 2 cases survived after receiving polyvalent anti-snake venom.
Chapter
Snakebite envenoming (SBE) leads to significant morbidity and mortality, resulting in over 90,000 deaths and approximately 400,000 amputations annually. In sub-Saharan Africa (SSA) alone, SBE accounts for over 30,000 deaths per annum. Since 2017, SBE has been classified as a priority Neglected Tropical Disease (NTD) by the World Health Organisation (WHO). The major species responsible for mortality from SBE within SSA are from the Bitis, Dendroaspis, Echis and Naja genera. Pharmacologically active toxins such as metalloproteinases, serine proteinases, 3-finger toxins, kunitz-type toxins, and phospholipase A2s are the primary snake venom components. These toxins induce cytotoxicity, coagulopathy, hemorrhage, and neurotoxicity in envenomed victims. Antivenom is currently the only available venom-specific treatment for SBE and contains purified equine or ovine polyclonal antibodies, collected from donor animals repeatedly immunized with low doses of adjuvanted venom. The resulting plasma or serum contains a high titre of specific antibodies, which can then be collected and stored until required. The purified antibodies are either whole IgG, monovalent fragment antibody (Fab) or divalent fragment antibody F(ab’)2. Despite pharmacokinetic and pharmacodynamic differences, all three are effective in the treatment of SBE. No antivenom is without adverse reactions but, the level of their impact and severity varies from benign early adverse reactions to the rarely occurring fatal anaphylactic shock. However, the major side effects are largely reversible with immediate administration of adrenaline and corticosteroids. There are 16 different antivenoms marketed within SSA, but the efficacy and safety profiles are only published for less than 50% of these products.
Article
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Access to safe, effective, quality-assured antivenom products that are tailored to endemic venomous snake species is a crucial component of recent coordinated efforts to reduce the global burden of snakebite envenoming. Multiple access barriers may affect the journey of antivenoms from manufacturers to the bedsides of patients. Our review describes the antivenom ecosystem at different levels and identifies solutions to overcome these challenges. At the global level, there is insufficient manufacturing output to meet clinical needs, notably for antivenoms intended for use in regions with a scarcity of producers. At national level, variable funding and deficient regulation of certain antivenom markets can lead to the procurement of substandard antivenom. This is particularly true when producers fail to seek registration of their products in the countries where they should be used, or where weak assessment frameworks allow registration without local clinical evaluation. Out-of-pocket expenses by snakebite victims are often the main source of financing antivenoms, which results in the underuse or under-dosing of antivenoms, and a preference for low-cost products regardless of efficacy. In resource-constrained rural areas, where the majority of victims are bitten, supply of antivenom in peripheral health facilities is often unreliable. Misconceptions about treatment of snakebite envenoming are common, further reducing demand for antivenom and exacerbating delays in reaching facilities equipped for antivenom use. Multifaceted interventions are needed to improve antivenom access in resource-limited settings. Particular attention should be paid to the comprehensive list of actions proposed within the WHO Strategy for Prevention and Control of Snakebite Envenoming.
Article
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Background: Snakebite envenoming (SBE) is a major problem in rural areas of West Africa (WA). Compared to other Neglected Tropical Diseases (NTD), the public health burden of SBE has not been well characterized. We estimated the impact of snakebite mortality and morbidity using the Disability Adjusted Life Years (DALYs) metrics for 16 countries in WA. Methods: We used the reported annual number of SB deaths and mean age at time of SB and converted these into years of life lost (YLL). Similarly, the years of life lived with disability (YLD) were estimated by multiplying the number of amputations by the respective disability weight of 0.13. Results: In WA, the annual cases of SB mortality and amputations ranged from 24 (95% Confidence Interval: 19-29) and 28 (17-48) respectively in Guinea-Bissau with the highest estimates of 1927 (1529-2333) and 2368 (1506-4043) respectively in Nigeria. We calculated that the annual DALYs associated with a SB death ranged from 1550 DALYs (95%CI: 1227-1873 DALYs) in Guinea Bissau to 124,484 DALYs (95%CI: 98,773-150,712 DALYs) in Nigeria. The annual DALYs associated with amputation for the two countries were 149 DALYs (95%CI: 91-256 DALYs) and 12,621 DALYs (95%CI: 8027-21,549 DALYs) respectively. The total burden of SBE was estimated at 319,874 DALYs (95% CI: 248,357-402,654 DALYs) in the 16 countries in WA. These estimates are similar, and in some instances even higher, than for other NTDs encountered in WA (e.g., Buruli ulcer, Echinococcosis, Intestinal Nematode Infections, Leishmaniasis, Onchocerchiasis, Trachoma and Trypanosomiasis) as reported in the Global Burden of Diseases 2010 (GBD). Conclusions: The public health burden of SBE in WA is very substantial and similar to other more widely recognized NTDs. Efforts and funding commensurate with its burden should be made available for the control of snakebite in the sub-region.
Article
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Background: Snakebite envenoming is a major public health problem throughout the rural tropics. Antivenom is effective in reducing mortality and remains the mainstay of therapy. This study aimed to determine the cost-effectiveness of using effective antivenoms for Snakebite envenoming in Nigeria. Methodology: Economic analysis was conducted from a public healthcare system perspective. Estimates of model inputs were obtained from the literature. Incremental Cost Effectiveness Ratios (ICERs) were quantified as deaths and Disability-Adjusted-Life-Years (DALY) averted from antivenom therapy. A decision analytic model was developed and analyzed with the following model base-case parameter estimates: type of snakes causing bites, antivenom effectiveness to prevent death, untreated mortality, risk of Early Adverse Reactions (EAR), mortality risk from EAR, mean age at bite and remaining life expectancy, and disability risk (amputation). End-user costs applied included: costs of diagnosing and monitoring envenoming, antivenom drug cost, supportive care, shipping/freezing antivenom, transportation to-and-from hospital and feeding costs while on admission, management of antivenom EAR and free alternative snakebite care for ineffective antivenom. Principal findings: We calculated a cost/death averted of ($2330.16) and cost/DALY averted of $99.61 discounted and $56.88 undiscounted. Varying antivenom effectiveness through the 95% confidence interval from 55% to 86% yield a cost/DALY averted of $137.02 to $86.61 respectively. Similarly, varying the prevalence of envenoming caused by carpet viper from 0% to 96% yield a cost/DALY averted of $254.18 to $78.25 respectively. More effective antivenoms and carpet viper envenoming rather than non-carpet viper envenoming were associated with lower cost/DALY averted. Conclusions/significance: Treatment of snakebite envenoming in Nigeria is cost-effective with a cost/death averted of $2330.16 and cost/DALY averted of $99.61 discounted, lower than the country's gross domestic product per capita of $1555 (2013). Expanding access to effective antivenoms to larger segments of the Nigerian population should be a considered a priority.
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Rotavirus gastroenteritis places a significant health and economic burden on Pakistan. To determine the public health impact of a national rotavirus vaccination program, we performed a cost-effectiveness study from the perspective of the health care system. A decision tree model was developed to assess the cost-effectiveness of a national vaccination program in Pakistan. Disease and cost burden with the program were compared to the current state. Disease parameters, vaccine-related costs, and medical treatment costs were based on published epidemiological and economic data, which were specific to Pakistan when possible. An annual birth cohort of children was followed for 5 years to model the public health impact of vaccination on health-related events and costs. The cost-effectiveness was assessed and quantified in cost (2012 US$) per disability-adjusted life-year (DALY) averted and cost per death averted. Sensitivity analyses were performed to assess the robustness of the incremental cost-effectiveness ratios (ICERs). The base case results showed vaccination prevented 1.2 million cases of rotavirus gastroenteritis, 93,000 outpatient visits, 43,000 hospitalizations, and 6700 deaths by 5 years of age for an annual birth cohort scaled from 6% current coverage to DPT3 levels (85%). The medical cost savings would be US$1.4 million from hospitalizations and US$200,000 from outpatient visit costs. The vaccination program would cost US$35 million at a vaccine price of US$5.00. The ICER was US$149.50 per DALY averted or US$4972 per death averted. Sensitivity analyses showed changes in case-fatality ratio, vaccine efficacy, and vaccine cost exerted the greatest influence on the ICER. Across a range of sensitivity analyses, a national rotavirus vaccination program was predicted to decrease health and economic burden due to rotavirus gastroenteritis in Pakistan by ∼40%. Vaccination was highly cost-effective in this context. As discussions of implementing the intervention intensify, future studies should address affordability, efficiency, and equity of vaccination introduction.
Article
The World Health Organisation defines good health as ‘a state of complete physical, mental and social well-being and not merely the absence of disease and infirmity’. People in the UK are healthier and living longer than ever before, with the major advances in life expectancy over the last century due mainly to public health innovations such as improvements in water quality and sewerage, and mass immunisation programmes which have reduced infectious diseases (DH,2010). This chapter looks not only at these improvements in life expectancy and lifestyles in the population, but changes in the prevalence of chronic sickness and disability and the impact on health services. There is also analysis of mental well-being and the effects of environmental factors such as winter temperature and infections on health.
Article
The spitting cobra, Naja nigricollis, is responsible for most cases of snake bite in the Malumfashi area. A survey revealed an incidence of N. nigricollis bite of 15 to 20 per 100 000 population per year in this part of northern Nigeria, with an estimated natural mortality of 5%. Of 106 victims of previous spitting cobra bite, only 8·5% were treated in hospital, and physical deformity as a result of necrosis from poisoning was present in 19%. This emphasized the fact that statistics based on hospital admissions seriously underestimate snake bite incidence, morbidity and mortality. Naja nigricollis is also important because of its ability to spit venom into the eyes of an assailant. Snake venom ophthalmia is usually regarded as having a benign course, but victims were described who had suffered more serious effects, including blindness. The epidemiology of human encounters with the spitting cobra is discussed, and it is shown that N. nigricollis is able to maintain a close association with man. The cobra is briefly compared with the carpet viper, Echis carinatus, which is more important in less densely populated and cultivated regions of Nigeria. The efficacy of antivenoms in N. nigricollis bite urgently requires clinical investigation.
Article
Background: Pre-medication has been used to protect against early adverse reactions (EAR) following antivenom administration after snakebite. Studies have evaluated its efficacy with variable results. Objective: The aim of the study was to conduct a systematic review and meta-analysis of published data to assess the effect of pre-medication on the risk of EAR. Methods: We conducted a search of MEDLINE, the Cochrane Database and various search engines/websites, searched handbooks, book chapters and peer-reviewed articles relating to clinical snakebite, and consulted experts in this field. The search was on published literature up to September 2010. A meta-analysis was conducted of all randomized and non-randomized studies of EAR following antivenom in snakebite that utilized either adrenaline (epinephrine)-containing or non-adrenaline (antihistamines, corticosteroids)containing pre-medications compared with control groups. We performed either random- or fixed-effects analysis based on the presence of heterogeneity as assessed with two tests, including the 12 statistic, and performed restricted analyses on data derived from randomized or non-randomized studies. Sensitivity analysis investigating the influence of single studies on overall estimates was conducted and we determined publication bias where detected in both of the two tests used for its assessment. Results: Three randomized and four non-randomized studies were selected for inclusion in this study. When all ten comparisons from the seven selected studies were combined (with a total of 434 subjects in the pre-medication groups and 399 subjects in the control groups), the overall summary risk ratio (RR) for EAR was 0.70(95% CI 0.50, 0.99; p=0.041; I(2)=66.5%). When analysis was restricted to only studies employing adrenaline-containing premedication, the combined summary RR was 0.32(95% CI 0.18, 0.58; p<0.0001; I(2)=9.5%). Results were not statistically significant when analyses were restricted to studies employing non-adrenaline-containing pre-medications, or cohort or randomized controlled designs. Analysis was limited by heterogeneity, paucity and quality of data. Conclusions: Findings are consistent with a substantial beneficial effect of adrenaline pre-medication, but a marginal benefit with the combination of pre-medications used against EAR could not be excluded. Future studies are recommended and they should explore possible synergism of broader combinations of drugs and effects of mode of antivenom administration in large randomized controlled trials. Meanwhile, highly purified antivenoms with less risk of EAR should be made available in the rural tropics.
Article
Snake bites are of major public health importance in Africa as causes of morbidity and mortality, but are largely neglected in health care planning. Echis carinatus is probably the most dangerous snake in the world, and is responsible of the majority of envenomation cases in West Africa. Among the components in snake venom are a number which have profound effects on haemostatic mechanisms and others with neurotoxicity. Antivenom immunotherapy is the only specific treatment available for the patients with envenomation. A comparison between three different antivenoms was performed in Goundi hospital in South Chad: the "IPSER AFRIQUE PASTEUR", the "Su polyvalent anti-snake venom serum - Central Africa" and the "FAV-Afrique immunoglobulin fragments". From January 1997 to December 2001, 288 patients enrolled in the study have been divided in three different cohorts on the basis of immunotherapy performed. The results demonstrate that the "Sii polyvalent anti-snake venom serum - Central Africa" seems completely ineffective in treatment of African snake bites; differences between "IPSER AFRIQUE PASTEUR" and "FAV-Afrique" could be ascribed to different corticosteroid treatment other than to differences in immunotherapy efficacy. If a lack of efficacy of corticos-teroid treatment is postulated the whole antivenom serum seems more active than immunoglobulin fragments.
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Decision making in health care means navigating through a complex and tangled web of diagnostic and therapeutic uncertainties, patient preferences and values, and costs. In addition, medical therapies may include side effects, surgery may lead to undesirable complications, and diagnostic technologies may produce inconclusive results. In many clinical and health policy decisions it is necessary to counterbalance benefits and risks, and to trade off competing objectives such as maximizing life expectancy vs optimizing quality of life vs minimizing the required resources. This textbook plots a clear course through these complex and conflicting variables. It clearly explains and illustrates tools for integrating quantitative evidence-based data and subjective outcome values in making clinical and health policy decisions. An accompanying CD-ROM features solutions to the exercises, PowerPoint® presentations of the illustrations, and sample models and tables.
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Background: The cost-effectiveness of early antiretroviral therapy (ART) in persons infected with human immunodeficiency virus (HIV) in serodiscordant couples is not known. Using a computer simulation of the progression of HIV infection and data from the HIV Prevention Trials Network 052 study, we projected the cost-effectiveness of early ART for such persons. Methods: For HIV-infected partners in serodiscordant couples in South Africa and India, we compared the early initiation of ART with delayed ART. Five-year and lifetime outcomes included cumulative HIV transmissions, life-years, costs, and cost-effectiveness. We classified early ART as very cost-effective if its incremental cost-effectiveness ratio was less than the annual per capita gross domestic product (GDP; $8,100 in South Africa and $1,500 in India), as cost-effective if the ratio was less than three times the GDP, and as cost-saving if it resulted in a decrease in total costs and an increase in life-years, as compared with delayed ART. Results: In South Africa, early ART prevented opportunistic diseases and was cost-saving over a 5-year period; over a lifetime, it was very cost-effective ($590 per life-year saved). In India, early ART was cost-effective ($1,800 per life-year saved) over a 5-year period and very cost-effective ($530 per life-year saved) over a lifetime. In both countries, early ART prevented HIV transmission over short periods, but longer survival attenuated this effect; the main driver of life-years saved was a clinical benefit for treated patients. Early ART remained very cost-effective over a lifetime under most modeled assumptions in the two countries. Conclusions: In South Africa, early ART was cost-saving over a 5-year period. In both South Africa and India, early ART was projected to be very cost-effective over a lifetime. With individual, public health, and economic benefits, there is a compelling case for early ART for serodiscordant couples in resource-limited settings. (Funded by the National Institute of Allergy and Infectious Diseases and others.).