Snakebite in KwaZulu-Natal: the burden of disease and prediction of risk of adverse outcomes.
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Date
2016
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Abstract
BACKGROUND
The total number of snakebites per annum in KwaZulu-Natal (KZN) is unknown. Yet it is
believed that the burden that snakebites place on hospitals in areas with a high incidence
of snakebite is significant. There are no official snakebite guidelines in South Africa or
KwaZulu-Natal. The result is non-uniform management practices and in many cases
inappropriate prescribing of antivenom, which may potentially be harmful given a high rate
of allergic reactions to antivenom. In order to standardise practice along evidence-based
lines, it is important to identify factors predictive of a poor outcome so that treatment can
be appropriately targeted at those individuals.
AIMS
1. To determine a figure for the annual incidence of snakebite, identify regional
variations in incidence and estimate the burden of snakebite on public hospitals in
the north-eastern province of KwaZulu-Natal, an area in which snakebite is
endemic.
2. To report a five-year prospective experience with snakebite in a highly endemic
area of South Africa and to identify factors predictive of severity.
3. To develop and validate a severity scoring system to facilitate the management of
snakebite in South Africa by allowing early identification of patients at increased
risk of a severe course, and thereby develop an improved algorithm for the
management of snakebite.
4. To determine the site of expansion accounting for the swelling in patients bitten by
a cytotoxic snake species, in particular to distinguish between muscle compartment
swelling and superficial swelling, and to determine the clinical utility of bedside
ultrasonic examination as a potential tool for identifying patients with possible
compartment syndrome.
METHODS
The work is reported as four sub-studies, using a selection of methodologies appropriate to
each, which are fully described in Chapters 2-7.
In order to determine incidence of snakebite, we applied a novel method whereby incidence
was extrapolated from antivenom supply data provided by the central provincial pharmacy
depot, with the appropriate conversion factor being determined from a stratified a sample
of 6 hospitals.
We analysed prospectively captured data on all patients admitted to Ngwelezane Hospi
Emergency Department from September 2008 to December 2013 with a diagnosis of
snakebite. Using the need for an active treatment intervention (ATI), which we defined as
antivenom administration or surgical intervention as a proxy for severity, we analysed our
data for factors present on admission which were predictive of severity. In a subsequent
study, we developed a severity score on a cohort of patients, which was then validated in a
separate and subsequent cohort of patients.
We developed a methodology for the assessment of depth of bite in patients bitten on a
limb whereby the ratio of the thickness of the deep muscle compartment and the
subcutaneous compartment of the bitten limb, measured by bedside ultrasound, were
expressed proportionally, and compared with the ratio on the unaffected limb. This
information was then used to identify the major site of swelling.
RESULTS
Incidence
We estimated that 11% (95% CI: 8-14%) of snakebite presentations to hospital resulted in
the administration of antivenom. By extrapolation, the overall incidence for KZN was
16/100 000. There was wide geographic variation, with the highest incidence, at 82/100
000 in the subtropical north east of the province. The estimated annual cost of snakebite in
KZN was between USD 1 135 782 and USD 2 877 314.
Analysis of a case series and prediction of severity
879 cases were analysed. Envenomation was identified in over two thirds of admissions.
Cytotoxic snakebites accounted for 98% of envenomations. Only 4 cases of haemotoxic
bleeding and 5 cases of neurotoxicity were admitted. Although we demonstrated a
significant correlation between severity and prolonged INR, reduced platelet count,
haemoglobin, reduced or elevated leucocyte count and elevated serum urea. However, their
use as predictors of severity was limited by poor sensitivity and specificity. Clinical factors
correlating with severity were the paediatric age group and a delayed presentation to
hospital.
In the prospective study, 146 of 879 snakebite admissions in the development cohort and
40 of 100 in the validation cohort reached the primary end point of an ATI. Six predictors
of risk for ATI were identified from the development cohort: age <14 years, delay to
admission >7 hours, white cell count > 10x109 cells/l, platelet count<92 x109/l,
haemoglobin <7.1 g/dl, INR >1.2. Each risk predictor was assigned a score of 1; ROC
curve analysis returned a value of more than 4 out of 6 as the optimal cut-off for prediction
of an ATI (AUC 0.804; 95% CI 0.758-0.84). Testing of the score on the validation cohort
produced a sensitivity of 22.5% and a specificity of 96.6%. The PPV and NPV were 81.8%
and 65.2% respectively.
Ultrasonic determination of the site of swelling in cytotoxic envenomation
The majority of bites were in the upper limb (27/42). Tissue expansion was noted in both
the sub-cutaneous and muscle compartments of the envenomed limbs. The site of swelling
was predominantly in the subcutaneous tissues, while swelling in muscle compartment was
limited (the mean expansion coefficient for subcutaneous tissues was 2.0 (CI: 1.7-2.3)
versus 1.06 (CI: 1.0-1.1) respectively). The difference between the groups was significant
(P<001). One case, confirmed as compartment syndrome, showed marked swelling in the
muscle group and stood out as a clear outlier in terms of the expansion coefficient.
CONCLUSIONS
The burden of snakebite is substantial, and is felt unequally across the province.
Furthermore, we propose that our method may be used to estimate the incidence of other
diseases treated with a standard regimen and for which incidence figures are otherwise
unknown.
Two-thirds of patients who present to hospital with snakebite in north-eastern South Africa
will have symptoms of envenomation, with the overwhelming majority manifesting
cytotoxicity. Bites by neurotoxic and haemotoxic species are rare. We have identified a
number of factors which may potentially be of value in predicting severity, but which are
on their own of insufficient accuracy to be reliable.
Basic ultrasound techniques may be used to identify the site and degree of tissue swelling
from cytotoxic envenomation. It is a non-invasive, painless procedure that can assist the
clinician to assess the injured limb and may also be of benefit to monitor the progression
of swelling.
Our scoring system, which we propose to name the Zululand Snakebite Severity Score
(ZSSS), is a useful adjunct to clinical assessment in managing snakebite. A patient with a
positive result has an 80% probability of progressing to the point where an ATI is indicated.
Its value is greatest in those patients who fall in the mild to moderate clinical category.
This score now requires validation on a wider scale across South Africa, to determine its
accuracy in areas other than those in which it was tested.
Description
Doctoral Degree. University of KwaZulu-Natal, Durban.