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Objective To quantify the public health and economic burden of endemic canine rabies in Africa and Asia. Methods Data from these regions were applied to a set of linked epidemiological and economic models. The human population at risk from endemic canine rabies was predicted using data on dog density, and human rabies deaths were estimated using a series of probability steps to determine the likelihood of clinical rabies developing in a person after being bitten by a dog suspected of having rabies. Model outputs on mortality and morbidity associated with rabies were used to calculate an improved disability-adjusted life year (DALY) score for the disease. The total societal cost incurred by the disease is presented. Findings Human mortality from endemic canine rabies was estimated to be 55 000 deaths per year (90% confidence interval (CI) = 24 000–93 000). Deaths due to rabies are responsible for 1.74 million DALYs lost each year (90% CI = 0.75–2.93). An additional 0.04 million DALYs are lost through morbidity and mortality following side-effects of nerve-tissue vaccines. The estimated annual cost of rabies is US$ 583.5 million (90% CI = US$ 540.1–626.3 million). Patient-borne costs for post-exposure treatment form the bulk of expenditure, accounting for nearly half the total costs of rabies. Conclusions Rabies remains an important yet neglected disease in Africa and Asia. Disparities in the affordability and accessibility of post-exposure treatment and risks of exposure to rabid dogs result in a skewed distribution of the disease burden across society, with the major impact falling on those living in poor rural communities, in particular children.
Keywords Rabies/mortality/economics; Dogs; Cost of illness; Disability evaluation; Health care costs; Probability; Models, Theoretical; Africa; Asia (source: MeSH, NLM). Mots clés Rage (Maladie)/mortalité/économie; Chien; Coût maladie; Evaluation incapacité; Coût soins médicaux; Probabilité; Modèle théorique; Afrique; Asie (source: MeSH, INSERM). Palabras clave Rabia/mortalidad/economía; Perros; Costo de la enfermedad; Evaluación de la incapacidad; Costos de la atención en salud; Probabilidad; Modelos teóricos; África; Asia (fuente: DeCS, BIREME).
Bulletin of the World Health Organization 2005;83:360-368.
Voir page 366 le résumé en français. En la página 366 figura un resumen en español.
Re-evaluating the burden of rabies in Africa and Asia Darryn L. Knobel,1 Sarah Cleaveland,1 Paul G. Coleman,2 Eric M. Fèvre,1 Martin I. Meltzer,3 M. Elizabeth G. Miranda,4 Alexandra Shaw,5 Jakob Zinsstag,6 & François-Xavier Meslin7
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1 Centre for Tropical Veterinary Medicine, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, Midlothian EH25 9RG, Scotland. Correspondence should be sent to Dr Knobel at this address (email:d.l.knobel@sms.ed.ac.uk). 2 London School of Hygiene and Tropical Medicine, Keppel Street, London, England. 3 Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. 4 Communicable Disease, Surveillance and Response, World Health Organization, Regional Office for the Western Pacific, Manila, Philippines. 5 AP Consultants, Andover SP11 7BA, England. 6 Swiss Tropical Institute, Basel, Switzerland. 7 World Health Organization, Geneva, Switzerland. Ref. No. 03-008862 (Submitted: 16 February 2004 – Final revised version received: 3 July 2004 – Accepted: 5 July 2004)
Introduction More than 99% of all human deaths from rabies occur in the developing world (1), and although effective and economical control measures are available (2, 3) , rabies remains a neglected disease throughout most of these countries (4, 5). A major fac- tor in the low level of political commitment to rabies control is a lack of accurate data on the true public health impact of the disease. It is widely recognized that the number of deaths officially reported greatly underestimates the true incidence of disease. Patients may not present to medical facilities for treat- ment of clinical disease; few cases receive laboratory confirma- tion; and clinical cases are often not reported by local authorities to central authorities (1, 6, 7).
These problems are not unique to rabies, and the recog- nized poor quality of much public health information from developing countries has prompted several investigations into the distribution of major infectious diseases and the mortality and morbidity attributable to them. Such studies are based on estimates of occurrence extrapolated from more readily quan- tifiable determinants of disease, such as vector distribution or host immunity (8–10). For rabies, a similar predictive approach has been used to estimate human deaths from rabies in the United Republic of Tanzania using a probability decision tree method to determine the likelihood of clinical rabies develop- ing in a person bitten by a dog suspected to be rabid (6). Dog bites are reported proportionately more frequently than human
361Bulletin of the World Health Organization | May 2005, 83 (5)
Research Darryn L. Knobel et al. Burden of rabies in Africa and Asia
cases of rabies and may provide an accessible data source from which human deaths from rabies can be inferred.
The objective of our study was to estimate the burden of rabies in Africa and Asia by applying data derived from these regions to this model and to thereby present a data-driven assessment of the human and economic costs of rabies in the developing world. We define Africa as all mainland countries on the continent plus Madagascar; Asia is defined as those countries falling under the WHO-defined South-East Asia Region and Western Pacific Region, including Pakistan. Only countries considered by WHO and the Office International des Epizooties as having endemic canine rabies were considered in this analysis. The list of all countries included in the study avail- able from http://www.vet.ed.ac.uk/ctvm/Research/Appendices/ appendices.html.
Methods Human rabies deaths Full details of the methods used in the dog-bite probability model have been published elsewhere (6). Briefly, the model recognizes that not all bites from rabid dogs result in infection and that not every infection leads to clinical signs and death. One of the principal factors influencing the outcome of a bite from a rabid dog is the location of the bite on the body (11, 12). The model uses the distribution of injuries on the body together with the likelihood of the patient receiving successful treatment to predict the outcomes of bites from rabid dogs. The model thus allows the incidence of bites from suspected rabid dogs among the human population considered to be at risk to be used as a determinant of the number of human deaths from rabies.
The human population at risk from canine rabies was taken as the number of people living in areas affected by ca- nine rabies where the density of the dog population exceeds the threshold density at which canine rabies is capable of be- ing maintained endemically. Dog-population densities were inferred from human densities derived from two regional population density datasets (13, 14) with adjustments made to account for population growth (15). Associated dog-popula- tion numbers were calculated by dividing human figures by the regional average ratio of humans to dogs, based on values given in Table 1. The threshold density for rabies persistence was taken as 4.5 dogs/km², based on predictions produced from data on rabies transmission in rural Kenya (16); these data are consistent with empirical observations from elsewhere in Africa (17–20). This density falls within the range of estimates of
rural dog-population densities (21–23), so the human popula- tion considered to be at risk was calculated using the regional rural ratios for humans to dogs. Implicit in this approach is the assumption that all human urban populations are at risk in rabies-affected areas.
Four basic scenarios were considered (Africa and Asia, both rural and urban); these reflect broad differences in fac- tors that influence rabies epidemiology and the treatment of people exposed to the disease. Initial parameter estimates were derived following a review of the relevant literature, including publications from peer-reviewed journals and grey literature sources. Parameter estimates and confidence distributions were then fixed using a three-stage consensus approach (as described in reference 9) within the WHO Burden of Rabies Working Group. First, a workshop was held during which parameter estimates were presented and discussed and preliminary predic- tions made using the model. Second, a comprehensive analysis using agreed upon estimates was conducted, and the model was validated against known data. Third, each participant was sent the results of this analysis, along with the data and assumptions. These were reviewed and adjusted as appropriate before final agreement was reached. The final model parameter estimates and distributions are presented in Table 2 (web version only, available at: http://www.who.int/bulletin).
For the analysis, Asia was subdivided into three units: China, India and Other Asia. Initial data sources and model validation indicated that parameter estimates for India and Other Asia were similar. However, preliminary model pre- dictions for China overestimated the number of deaths by one order of magnitude when these same estimates were used compared with the 1000 deaths suggested by expert opinion. The discrepancy is possibly explained by the use of post-exposure treatment in China: the country accounts for two-thirds (5 million cases) of total post-exposure treatment (PET) used in Asia (24), and the locally-produced tissue-culture vaccine is safe and relatively inexpensive (25). These factors suggest that PET for rabies is more accessible and utilized more frequently in China than in the rest of Asia. To account for this in the model, the probability of a person bitten by a suspected rabid dog and receiving PET was assumed to be equally high in both urban and rural settings in China (minimum = 95%; most likely = 97%; maximum = 100%). In light of the paucity of data for China, the model’s predictions for this country should be treated with caution.
The model was arrayed as a spreadsheet template (using Microsoft Excel 2000, Microsoft Inc., Redmond, WA). Uncer- tainty in parameter estimates, and inherent parameter vari- ability due to between-country differences, were incorporated
Table 1. Mean human:dog ratio for Africa and Asia (determined from sources available from: http://www.vet.ed.ac.uk/ctvm/Research/ Appendices/appendices.html)
Regiona
Human:dog ratio Africa Asia China
Urban Rural Urban Rural Urban Rural
Mean ratiob 21.2 (12.5–37.1) 7.4 (5.7–9.7) 7.5 (4.8–10.1) 14.3(0–45.0) NAc NA Mean ratio for region 12.3 (11.2–20.6) 9.5 (4.5–14.6) 48.3 (0–147.0)
a Insufficient data were available to calculate a separate figure for India and for rural China versus urban China. b Figures in parentheses are 95% confidence intervals. c NA = not available.
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Research Burden of rabies in Africa and Asia Darryn L. Knobel et al.
into the model by assigning confidence distributions to input parameters. Parameter distributions were sampled iteratively (until convergence at < 1.5%) using a Monte Carlo simulation procedure (@Risk Pro 4.5, Palisade Corp., Newfield, NY). Model predictions are reported using the means of the resulting prob- ability distributions, with the 5th and 95th percentiles (90% confidence intervals) as the lower and upper bounds, respectively. A full account of the technical details of the model, including results of the sensitivity analysis, is available from: http://www. vet.ed.ac.uk/ctvm/Research/Appendices/appendices.html 3.
Disability-adjusted life year score The disability-adjusted life year (DALY) score is a standardized, comparative measure of the burden of disease. The DALY score for a particular condition is a composite score of the years of life lost (YLL) due to premature mortality and the years of life lived with a disability (YLD) caused by the condition (26). To calculate a DALY score for rabies the following components
were considered: a direct DALY score derived from mortality due to the disease and an indirect DALY score, taking into ac- count morbidity and mortality following side-effects of nerve- tissue vaccines.
Direct DALY score The output of the predictive model provided the estimated annual number of deaths due to rabies. Age-structures and sex- structures of rabies cases were obtained from seven reported studies (27–33). All parameter estimates and data sources re- lated to the calculation of the rabies DALY score are given in Table 3 (web version only, available at: http://www.who.int/ bulletin). Using these parameter estimates, a DALY score for rabies was determined using previously described methods (26, 34). Parameter variability was again incorporated by assign- ing confidence distributions and using simulation software as described above. The 5th and 95th percentiles were used as the lower and upper bounds for the predicted scores.
Table 4. Direct (medical) post-exposure treatment costing data and sources (available from: http://www.vet.ed.ac.uk/ctvm/Research/ Appendices/appendices.html)
Estimate
Parameter Africa Asia Source
Patient numbers No. PETa cases per year 200 000 7 500 000 11–14, 23–27 No. (%) PET patients receiving tissue-culture vaccines 180 000 (90) 5 025 000 (67) 11–14, 23–27 No. (%) of patients receiving tissue-culture vaccine intramuscularly 180 000 (100) 4 874 250 (97) 11–14, 23–27 No. (%) of patients receiving tissue-culture vaccine intradermally 0 (0) 150 750 (3) 11–14, 23–27 No. (%) PET patients receiving nerve-tissue vaccines 20 000 (10) 2 475 000 (33) 11–14, 23–27 No. (%) PET patients receiving rabies immunoglobulin 2 000 (1) 450 000 (6) 11–14, 23–27 No. (%) PET patients receiving human rabies immunoglobulin 0 (0) 45 000 (10) No. (%) PET patients receiving equine rabies immunoglobulin 2 000 (100) 405 000 (90)
Costs Common costs Material costs per injection (includes needles, syringes, swabs, etc.) US$ 0.10 E. Miranda unpublished data, 2003 Overhead costs per PET visit (includes anti-rabies clinic staff US$ 0.50 39 salaries and administration costs)
Tissue-culture vaccine costs Intramuscular vaccination Vaccine cost per dose US$ 10.00 WHO Procurement Services, personal communication, 2003 Visits per patient 3 40 Injections per patient 3 Assuming standard Essen regimen Intradermal vaccination Vaccine cost per dose US$ 2.50 WHO Procurement Services, personal communication, 2003 Visits per patient 3 E. Miranda unpublished data, 2003 Injections per patient 6 Assuming Thai Red Cross regimen
Nerve-tissue vaccine costs Vaccine cost per dose US$ 0.40 7 Visits per patient 7 33 Injections per patient 7 Assuming standard regimen
Rabies immunoglobulin Human rabies immunoglobulin cost per dose US$ 110.00 WHO Procurement Services, personal communication, 2003 Equine rabies immunoglobulin cost per dose US$ 25.00 WHO Procurement Services, personal communication, 2003
a PET = post-exposure treatment.
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Research Darryn L. Knobel et al. Burden of rabies in Africa and Asia
Table 5. Indirect (patient) costs of post-exposure treatment and other costs associated with rabies. Data sources are available from: http://www.vet.ed.ac.uk/ctvm/Research/Appendices/appendices.html
Estimate
Parameter Africa Asia Source
Indirect PETa costs No. of PET patient visits 680 000 32 400 000 Calculated from Table 4 Proportion of visits accompanied by an adult 0.4 0.4 2, 16 Total No. of visits (patients plus those accompanying them) 952 000 45 360 000 Calculated
Income loss No. of working days lost per person per PET visit 0.5 0.5 15 Daily per capita Gross National Income US$ 1.87 US$ 3.50 41 Income loss per person per PET visit US$ 0.94 US$ 1.75 Calculated
Transport costs Transport costs per person per visit US$ 2.00 US$ 3.80 40, M. Kaare, personal communication, 2002 Dog rabies costs Vaccination costs No. dogs vaccinated annually 6 700 000 40 000 000 11–14, 23–27 Cost per dog vaccinated US$ 1.30 US$ 1.30 42
Population control costs No. dogs killed annually 200 000 5 000 000 11–14, 23–27 Cost per dog killed US$ 5.00 US$ 5.00 43
Livestock losses Total no. cattle 230 000 000 423 000 000 44 Rabies incidence rate/100 000 cattle 5 5 11–14, 23–27 Annual no. of cattle deaths from rabies 11 500 21 150 Calculated Cost per head of cattle US$ 150.00 US$ 500.00 A. Shaw, unpublished data, 2002
Surveillance costs No. rabies diagnostic tests per year 5 300 16 500 11–14, 23–27 Cost per test US$ 5.68 US$ 5.68 45
a PET = post-exposure treatment.
Indirect DALY burden Evidence suggests that non-rabies induced morbidity and mor- tality may constitute a sizeable proportion of the rabies burden in developing countries. Approximately one-third of all human rabies post-exposure treatments are carried out using crude nerve-tissue vaccines (35), despite the occurrence of severe and sometimes fatal allergic encephalomyelitic reactions (36–38). Nerve-tissue vaccines were classified into two groups based on differing incidence rates and clinicopathological signs of adverse reactions (37, 38). These were the Semple type (made from phenol-treated sheep-brain or goat-brain tissue) and vac- cines derived from suckling-mouse brain. For the purpose of this preliminary analysis, disability weights for post-vaccination neurological reactions, used in the calculation of the YLDs, were taken as those reported for similar conditions by Murray & Lopez (39) (Table 3). The use of equivalent disability weights represents an admittedly crude first attempt to determine a YLD component of the DALY score for rabies; future attempts would benefit from a formal disability weighting procedure.
The economic burden of rabies The mortality rate and DALY score provide estimates of the burden of disease on human health. A second component of the impact of disease is the economic cost incurred by society as
a result of the disease. The costs due to rabies were considered under the following categories: • direct (medical) human costs from post-exposure treatment • indirect (patient) costs from post-exposure treatment • costs to control rabies among dogs • livestock losses • surveillance costs.
Table 4 and Table 5 give a breakdown of the costing data used in the economic analysis.
For this analysis, direct medical costs included the cost of biologicals (rabies vaccines and immunoglobulin) and the cost of their administration, including materials and staff salaries. Indirect costs included out-of-pocket expenses for patients, such as transport costs to and from rabies-treatment centres, and loss of income while receiving treatment (40). Costs asso- ciated with the treatment of dog bites and the administration of antibiotics and tetanus immunizations were not included. Due to the erratic frequency of reporting, national numbers of patients receiving post-exposure treatment annually were aver- aged over a period of 5 years (1996–2000). Countries for which no reports could be found for this period were considered not to have treated any patients. Post-exposure treatment was catego- rized by administration route (intramuscular or intradermal) on
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Research Burden of rabies in Africa and Asia Darryn L. Knobel et al.
Table 6. Estimated human mortality caused by canine rabies in Africa and Asia
Asia
Model output India China Other Asia Africa
Urban Rural Urban Rural Urban Rural Urban Rural
Total population (millions) 284.7 732.2 459.1 816.1 295.7 525.4 294.2 498.1 Population at risk (millions) 284.7 710.4 459.1 498.3 295.7 409.1 294.2 340.1 No. bites from suspected rabid dogs (thousands) 409.4 893.4 660.1 626.7 425.2 514.5 374.3 427.8 No. of rabies deathsa 1 058 18 201 1 324 1 257 853 8 135 5 886 17 937 No. deaths/100 000 people 0.37 2.49 0.29 0.15 0.29 1.55 2.00 3.60
No. subregional deathsb 19 713 2336 9 489 (4 192–39 733) (565–5 049) (2 281–19 503)
No. regional deaths 31 539 (8 149–61 425) 23 705 (6 903–45 932)
Total no. deaths 55 270 (23 910–93 057) Overall no. deaths/100 000 people 1.38 (0.60–2.33) Predicted deaths in the absence of any 327 160 (166 904–525 427) post-exposure treatment
a Rabies deaths are the means of output probability distributions calculated independently and may therefore not sum exactly. b Figures in parentheses are the 5th and 95th percentiles of output probability distributions.
the basis that intradermal vaccination reduces costs by 60–80% compared to the standard intramuscular regimen (41, 42). The total number of vaccine doses (i.e. injections) administered and the total number of visits made to rabies-treatment centres were derived from national estimates of the proportion of patients receiving treatment who were vaccinated with each schedule, after adjustment to account for patient drop-out during the course of treatment. Few published accounts dealing with treatment-seeking behaviour and compliance could be found so conservative estimates were made on the average number of visits per schedule: 3 instead of 5 for the Essen and Thai Red Cross regimens and 7 instead of 10–21 for the nerve-tissue vaccine schedules. The proportion of patients receiving the Zagreb schedule, based on available data, was negligible at the scale of this study. It was assumed that all children aged < 16 years were accompanied by an adult. Assessment of transport costs and income loss include costs to both patients and those accompanying them.
Annual dog vaccination figures could not be found for all countries so the average vaccination coverage of the estimated national dog population was calculated for those countries that submitted reports between 1996 and 2000 (10.3% in Africa
and 9.7% in Asia); this figure was then applied to all countries in the region to predict the total number of dogs vaccinated. Cost predictions were based on the use of a central-point vac- cination system. Vaccination costs per dog include all com- ponents of campaign organization, public awareness efforts, and biological and material costs. Indirect costs borne by dog owners were not included in the analysis.
Livestock losses to rabies can be significant; however, there are few published estimates of rabies incidence in livestock. Sub- mission of cattle specimens to central veterinary laboratories reveals an annual incidence of 0.5–2 deaths/100 000 head of cattle; this is certain to be a gross underestimate. Assuming a rate of underreporting of 10, and using the lower end of the range of incidence rates to exclude transmission from wildlife reservoirs, an estimated incidence of 5 deaths/100 000 cattle is obtained.
Insufficient data were available to enable parameter vari- ability to be explicitly incorporated into the economic analysis. An attempt was made to model the uncertainty surrounding parameter estimates by inputting estimates as triangular dis- tributions (43), with the maxima and minima set as ± 10% of each parameter’s values.
Table 7. Estimated disability-adjusted life year (DALY) score for rabies in Africa and Asia
DALY scorea
Component Africa Asia Total
Rabies deathsb 747 558 (217 690–1 448 514) 994 607 (257 275–1 939 125) 1 743 015 (754 019–2 934 656) Nerve-tissue vaccine reactions 360 (142–586) 44 525 (17 585–72 575) 44 885 (17 727–73 162) Total 747 918 (217 954–1 449 014) 1 039 119 (302 324–1 983 646) 1 787 886 (799 615–2 984 109) Total (assuming no post- 9 504 237 (4 848 684–15 264 050) exposure treatment)
a DALY scores are the means of output probability distributions calculated independently and may therefore not sum exactly. b Figures in parentheses are the 5th and 95th percentiles of output probability distributions.
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Research Darryn L. Knobel et al. Burden of rabies in Africa and Asia
Results Model outputs The results of the predicted human mortality, disability- adjusted life year score and economic burden of rabies are presented in Table 6, Table 7 and Table 8, respectively. The pre- dicted number of human deaths remained within the reported confidence limits when the threshold dog density was doubled to 9 dogs/km² (46 000; 90% confidence interval (CI) = 19 000–79 000). Setting the threshold density to 0 (i.e. assuming that all people are at risk within areas where canine rabies is endemic) also had little effect on the model: in such a scenario the predicted number of deaths was 67 000 (90% CI = 30 000–110 000).
Discussion This paper provides the results of the first attempt at a quan- titative prediction of the burden of rabies in Africa and Asia. Although we attempted to incorporate the entire range of parameter variability, the final result is still likely to be an un- derestimate of total mortality and morbidity caused by rabies in these regions. Only deaths due to canine rabies were assessed, omitting that fraction of human cases resulting from exposure to rabid wild animals (35). In determining the number of hu- mans at risk, only populations in areas where canine rabies is endemic were included. This ignores the possibility of sporadic outbreaks in areas of low dog density or the introduction of the virus into a previously rabies-free population, as happened on the Indonesian island of Flores in 1997 (44).
The results of the modelling are consistent with those of other studies that have estimated the true incidence of rabies at a national level. The recent national survey by the Association for the Prevention and Control of Rabies in India (45) esti- mated a total of 18 500 human deaths from rabies in the coun- try each year, which is close to the predicted figure of 19 700 in this report. The model also estimated the annual number of patients receiving post-exposure treatment in India as 1.07 million, which again is in good agreement with the reported national estimate of 1.1 million (46). The model’s predictions for China are less consistent: the predicted number of patients
receiving post-exposure treatment is 1.25 million which is four times lower than national estimates of 5 million; the predicted number of deaths remains more than double that estimated by expert opinion. However, recent figures communicated by the Chinese authorities are more in line with the model’s predictions (Personal communication, 2004): more than 2000 cases of rabies in humans were reported in 2003, with an 80% increase in the first quarter of 2004 (compared to the same period in 2003). Given the gross underreporting associated with rabies deaths, this suggests that the model may in fact be an underestimate of the true number, and the original predic- tion of approximately 10 000 deaths may prove more realistic. Detailed studies on dog ecology and rabies epidemiology and treatment in China are necessary to resolve this.
WHO’s 1999 World survey of rabies (35) reported 1722 human rabies deaths from the study regions: 147 in Africa and 1575 in Asia. The predicted figure of 55 000 deaths suggests that only 3% of human rabies deaths are recorded by central health authorities, a rate of underreporting of between 20 times (Asia) and 160 times (Africa). This is in agreement with findings from other studies using active surveillance methods that found the incidence of human rabies is up to 100 times greater than what is officially recorded (6, 47).
The burden of rabies is not evenly distributed across all sectors of society but is influenced by age-related and socioeco- nomic factors. The total cost (direct medical costs and indirect patient costs, excluding those of any accompanying people) of an average post-exposure treatment course as determined in this study is US$ 39.57 in Africa and US$ 49.41 in Asia. This amounts to a substantial fraction of annual per capita gross national income (GNI): 5.80% for the average person living in Africa and 3.87% for someone living in Asia. Even if medical costs are fully subsidized by the government, out-of-pocket pa- tient expenses still comprise 1.5–2% of per capita GNI. Often government subsidies extend only to the provision of cheaper nerve-tissue vaccines, with tissue-culture vaccines being pro- vided only to those patients able to pay for them. There is there- fore an income-related risk factor in exposure to the side-effects of nerve-tissue vaccines. This is compounded by occupational
Table 8. Estimated annual expenditure due to rabies
Costa
Category Africa Asia Total
PET costsb, c 9.1 (8.2–10.0) 475.9 (435.0–520.5) 485.0 (443.4–530.1) Direct (medical) 5.9 (5.2–6.6) 190.3 (171.4–210.5) 196.2 (176.9–216.7) Indirect (patient) 3.2 (2.9–3.5) 285.6 (259.2–312.1) 288.7 (262.2–315.4) Income loss 1.3 (1.2–1.4) 113.5 (104.4–122.9) 114.7 (105.7–124.1) Transport costs 1.9 (1.7–2.1) 172.1 (154.1–190.5) 174.0 (155.9–192.5)
Dog rabies control costs 9.7 (8.8–10.6) 77.0 (71.5–82.3) 86.7 (80.7–92.8) Vaccination costs 8.7 (7.8–9.6) 52.0 (47.1–57.0) 60.7 (55.4–66.3) Population control costs 1.0 (0.9–1.1) 25.0 (22.5–27.5) 26.0 (23.4–28.6) Livestock losses 1.7 (1.5–1.9) 10.5 (9.4–11.8) 12.3 (11.0–13.7) Surveillance costs 0.03 (0.026–0.032) 0.09 (0.08–0.10) 0.12 (0.11–0.13)
Total 20.5 (19.3–21.8) 563.0 (520.0–605.8) 583.5 (540.1–626.3)
a Costs are in millions of US$. b PET = post-exposure treatment. c Figures in parentheses are the 5th and 95th percentiles of output probability distributions.
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Research Burden of rabies in Africa and Asia Darryn L. Knobel et al.
and socioeconomic risk factors in the initial exposure to infec- tion, further skewing the burden of rabies towards those sectors of society least able to bear it (45, 48). The results of our study predict that there will be five times more rabies deaths in rural areas than in urban areas. Children in particular are at a higher risk of exposure to rabid dogs. Typically, 30–50% of those re- ceiving post-exposure treatment are children aged < 16 years (6, 49). Children are also more likely to suffer multiple bites and bites to the face and head, both of which carry a higher risk of contracting rabies (31, 50).
Rabies continues to impact human health despite the existence of proven cost-effective control measures. Vaccinating domestic dogs against rabies results in a significant reduction in the incidence of bites among the human population from dogs suspected to be rabid, and this control strategy has been shown
to be the most cost-effective in the medium–long term (4); costs are typically recouped within 5–10 years, mainly through decreased expenditure on human post-exposure treatment. O
Acknowledgements The authors thank Dr Alex Wandeler and Dr Ursula Kayali for their comments on an earlier draft of this manuscript and Dr Deborah Briggs for useful discussions.
Funding: DK and SC are supported by a grant from the Well- come Trust. JZ is supported by NCCR “North-South” IP-4, which is funded by the Swiss National Science Foundation and the Swiss Development Cooperation.
Competing interests: none declared.
Résumé
Réévaluation de la charge que représente la rage en Afrique et en Asie Objectif Quantifier le fardeau économique et la charge pour la santé publique que représente la rage canine endémique en Afrique et en Asie. Méthodes Les données provenant de ces régions ont été appliquées à un ensemble de modèles épidémiologiques et économiques associés. On a estimé le nombre de personnes qui seraient exposées à la rage canine endémique à partir des données de la densité canine et le nombre des décès humains dus à la rage au moyen d’un modèle de probabilité pas à pas utilisé pour déterminer la probabilité qu’une personne mordue par un chien présumé enragé présente la maladie. La mortalité et la morbidité liées à la rage fournies par les modèles ont été utilisées pour affiner le calcul des années de vie ajustées sur l’incapacité (DALY) pour la maladie. Le coût social total de la maladie est présenté. Résultats On a estimé à 55 000 [intervalle de confiance (IC) à 90% = 24 000-93 000] le nombre annuel des décès humains dus à la rage canine endémique. Les décès dus à la rage sont responsables
de 1,74 million d’années de vie ajustées sur l’incapacité perdues chaque année (IC à 90% = 0,75-2,93). Quelque 0,04 million d’années de vie ajustées sur l’incapacité supplémentaires sont en outre perdues du fait de la morbidité et de la mortalité dues aux effets secondaires des vaccins préparés sur tissu nerveux. Le coût annuel estimatif de la rage est de US$ 583,5 millions (IC à 90% = US$ 540,1 – 626,3 millions). Le coût des traitements post-exposition supporté par les malades constitue l’essentiel des dépenses, soit près de la moitié du coût total de la rage. Conclusion La rage reste une maladie importante mais négligée en Afrique et en Asie. Les écarts aux plans de l’accessibilité financière et physique du traitement post-exposition et du risque d’exposition aux chiens enragés rendent inégale la distribution de la charge de morbidité dans la société, les personnes les plus touchées étant les habitants des communautés rurales défavorisées, et en particulier les enfants.
Resumen
Reevaluación de la carga de rabia en África y Asia Objetivo Cuantificar la carga que supone la rabia canina endémica en África y Asia en términos económicos y de salud pública. Métodos Se aplicaron datos de esas regiones a un conjunto de modelos epidemiológicos y económicos relacionados. La población humana expuesta al riesgo de sufrir rabia canina endémica se predijo a partir de los datos disponibles sobre la densidad de perros, y las defunciones por rabia humana se estimaron usando una serie de pasos probabilísticos para determinar el riesgo de aparición de rabia clínica en una persona que hubiera sido mordida por un perro sospechoso de albergar rabia. Los resultados modelizados sobre la mortalidad y la morbilidad asociadas a la rabia se usaron para obtener un valor mejorado de los años de vida ajustados en función de la discapacidad (AVAD) para la enfermedad. Se presenta el costo social total asociado a esta dolencia. Resultados La mortalidad humana por rabia canina endémica se estimó en 55 000 defunciones anuales (intervalo de confianza
(IC) del 90% = 24 000-93 000). Las defunciones por rabia causan unas pérdidas de 1,74 millones de AVAD cada año (IC90% = 0,75- 2,93). Otros 40 000 AVAD se pierden como consecuencia de la morbilidad y mortalidad asociadas a los efectos colaterales de las vacunas obtenidas con tejido nervioso. El costo anual estimado de la rabia asciende a US$ 583,5 millones (IC90% = US$ 540,1 - 626,3 millones). Los costos del tratamiento postexposición asumidos por los pacientes constituyen el grueso del gasto correspondiente, pues suponen casi la mitad del costo total de la rabia. Conclusión La rabia sigue siendo una importante y sin embargo descuidada enfermedad en África y Asia. Las disparidades en la asequibilidad y accesibilidad del tratamiento postexposición y en el riesgo de exposición a perros rabiosos se traducen en una distribución asimétrica de la carga de morbilidad en la sociedad, de tal manera que el impacto principal de la enfermedad recae en los habitantes de las comunidades rurales pobres, sobre todo en los niños.
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Table 2. Parameter estimates, probability distributions and data sources used in the prediction of human deaths from rabies from injury data on dog bites (data sources available from: http://www.vet.ed.ac.uk/ctvm/Research/Appendices/appendices.html)
Parameter estimates
Description Africa Asia
Urban Rural Urban Rural
Annual incidence of Trigen:a 1–6 suspect bites from Practical minimum 6 6 50 15 rabid dogs per Most likely 100 100 120 100 100 000 humans Practical maximum 227 227 250 250 Bottom and top percentiles 0%; 95% 0%; 95% 5%; 95% 5%; 95%
P10 Probability of an Trigen: 2, 7 individual bitten by a Practical minimum 0.80 0.55 0.95 0.70 dog suspected to be Most likely 0.85 0.60 .097 0.75 rabid receiving Practical maximum 0.90 0.60 1.00 0.80 successful post- Bottom and top percentiles 5%; 95% 5%; 95% 10%; 100% 10%; 90% exposure treatment
P1 Probability of a Beta:b India Other Asia 2, 3, 8–15 suspected rabid dog No. of suspect dogs examined 9 285 5 863 59 588 being confirmed No. confirmed rabid 5 291 2 906 22 923 rabid on laboratory P1 0.64 0.50 0.38 diagnosis
P2 Probability of a bite Point probability 0.07 2, 16, 17, to the head or neck E. Miranda unpublished data, 2003
P3 Probability of a bite to Point probability 0.38 2, 16, 17, the upper extremity E. Miranda (arm or hand) unpublished data, 2003
P4 Probability of a bite Point probability 0.06 2, 16, 17, injury to the trunk of E. Miranda the body unpublished data 2003
P5 Probability of a bite to Point probability 0.49 2, 16, 17, the lower extremity E. Miranda (leg or foot) unpublished data, 2003
P6 Probability of Triangular: 18–21 developing rabies Minimum 0.30 following a bite to the Most likely 0.45 head by a rabid dog Maximum 0.60
P7 Probability of Triangular: 18–21 developing rabies Minimum 0.15 following a bite to an Most likely 0.28 upper extremity by a Maximum 0.40 rabid dog
P8 Probability of Triangular: 18–21 developing rabies Minimum 0 following a bite to the Most likely 0.05 trunk by a rabid dog Maximum 0.10
P9 Probability of Triangular: 18–21 developing rabies Minimum 0 following a bite to a Most likely 0.05 lower extremity by Maximum 0.10 a rabid dog
a The Trigen distribution avoids the use of absolute maxima and minima by allowing the specification of a likely range for the parameter together with an estimation of the probability that the parameter will fall outside this range (top and bottom percentiles). b The Beta distribution is a binomial process allowing estimation of the probability of success p, given s successes from n trials. Assuming a non-informative Uniform (0, 1) prior, the Beta distribution takes the form p = Beta (s + 1, n – s + 1). See reference 22 for a discussion of commonly used probability distributions.
Probability distribution
Param- eter
Source of data
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Research Burden of rabies in Africa and Asia Darryn L. Knobel et al.
Table 3. Parameter estimates and data sources used to calculate the disability-adjusted life year (DALY) score for rabies (data sources available from: http://www.vet.ed.ac.uk/ctvm/Research/Appendices/appendices.html)
Estimate
Parameter Africa Asia Source
No. human rabies deaths per yeara 23 788 (7 280–44 112) 30 942 (6 017–61 657) Model output (Table 3)
No. PETb cases per year 200 000 7 500 000 12–14, 23–27
No. (%) of PET patients receiving nerve-tissue vaccines 20 000 (10) 2 475 000 (33) 12–14, 23–27
No. (%) of NTVc patients receiving Semple-type 16 000 (80) 1 980 000 (80) 12–14, 23–27 nerve-tissue vaccine
No. (%) of NTV patients receiving suckling-mouse brain 4 000 (20) 495 000 (20) 12–14, 23–27 nerve tissue vaccine
Rate of neurological complications per 100 patients Triangular: 16, 28–31 receiving Semple vaccine Minimum = 0.035; Most likely = 0.40; Maximum = 0.83
Case–fatality rate for cases of Semple neurological 0.17 30, 32, 33 complications
Disability weight for Semple neurological complications 0.613 34 (disability weight for an episode of bacterial meningitis)
Disability duration for Semple neurological complications Triangular: 35 Minimum = 1 day; Most likely = 8 days; Maximum = 1 year
Rate of neurological complications per 100 patients Triangular: 29, 31, 35, 36 receiving suckling-mouse brain vaccine Minimum = 0.013; Most likely = 0.03; Maximum = 0.08
Case–fatality rate for cases of neurological complications 0.22 29 from suckling-mouse brain vaccine
Disability weight for suckling-mouse brain neurological 0.725 34 (disability weight complications for an injured spinal cord)
Disability duration for suckling-mouse brain neurological 200 days 37 complications
DALY formula parameters Discount rate r 0.03 38 Age-weighting correction constant C 0.1658 38 Age-weighting function constant 0.04 38
a Values in parentheses are 90% confidence intervals. b PET = post-exposure treatment. c NTV = nerve-tissue vaccine.