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Deaths from Symptomatically Identifiable Furious Rabies in India: A Nationally Representative Mortality Survey
research-article
Author(s):
Wilson Suraweera
1 ,
Shaun K. Morris
1
,
2 ,
Rajesh Kumar
3 ,
David A. Warrell
4 ,
Mary J. Warrell
5 ,
Prabhat Jha
1
,
* ,
for the Million Death Study Collaborators
Publication date (Electronic):
4 October 2012
Journal:
PLoS Neglected Tropical Diseases
Publisher:
Public Library of Science
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Abstract
Background
It is estimated that India has more deaths from rabies than any other country. However, existing estimates are indirect and rely on non-representative studies.
Methods and Principal Findings
We examined rabies deaths in the ongoing Million Death Study (MDS), a representative survey of over 122,000 deaths in India that uses enhanced types of verbal autopsy. We estimated the age-specific mortality rates of symptomatically identifiable furious rabies and its geographic and demographic distributions. A total of 140 deaths in our sample were caused by rabies, suggesting that in 2005 there were 12,700 (99% CI 10,000 to 15,500) symptomatically identifiable furious rabies deaths in India. Most rabies deaths were in males (62%), in rural areas (91%), and in children below the age of 15 years (50%). The overall rabies mortality rate was 1.1 deaths per 100,000 population (99%CI 0.9 to 1.4). One third of the national rabies deaths were found in Uttar Pradesh (4,300) and nearly three quarters (8,900) were in 7 central and south-eastern states: Chhattisgarh, Uttar Pradesh, Odisha, Andhra Pradesh, Bihar, Assam, and Madhya Pradesh.
Conclusions and Significance
Rabies remains an avoidable cause of death in India. As verbal autopsy is not likely to identify atypical or paralytic forms of rabies, our figure of 12,700 deaths due to classic and clinically identifiable furious rabies underestimates the total number of deaths due to this virus. The concentrated geographic distribution of rabies in India suggests that a significant reduction in the number of deaths or potentially even elimination of rabies deaths is possible.
Author Summary
Rabies, a disease of antiquity, has been partially controlled in many countries and eliminated in a few. However, according to the World Health Organization, rabies continues to kill thousands of people in India each year, more than in any other country. We used an enhanced type of verbal autopsy (a structured interview of the relatives or close associates of the dead by non-medical staff with central medical coding by at least two doctors) to identify the causes of over 122,000 deaths in a large scale, representative sample in India in 2001–03. Using these data, we estimate that in 2005 approximately 12,700 people died from symptomatically identifiable furious rabies. Because verbal autopsy is not able to identify atypical presentations of rabies, our figure underestimates the actual number of rabies deaths in India. The majority of rabies deaths occurred in males, in rural areas, in children below the age of 15 years, and in a few states. The concentrated geographic distribution of rabies in India suggests that targeting with preventive campaigns including vaccination of animals and post exposure vaccination of humans might achieve a significant reduction in the number of deaths or potentially even elimination of deaths from this disease.
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Most cited references29
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Snakebite Mortality in India: A Nationally Representative Mortality Survey
Introduction Alexander the Great invaded India in 326 BC, and was greatly impressed by the skill of Indian physicians; especially in the treatment of snakebites [1]. Since then, India has remained notorious for its venomous snakes and the effects of their bites. With its surrounding seas, India is inhabited by more than 60 species of venomous snakes – some of which are abundant and can cause severe envenoming [2]. Spectacled cobra (Naja naja), common krait (Bungarus caeruleus), saw-scaled viper (Echis carinatus) and Russell's viper (Daboia russelii) have long been recognised as the most important, but other species may cause fatal snakebites in particular areas, such as the central Asian cobra (Naja oxiana) in the far north-west, monocellate cobra (N. kaouthia) in the north-east, greater black krait (B. niger) in the far north-east, Wall's and Sind kraits (B. walli and B. sindanus) in the east and west and hump-nosed pit-viper (Hypnale hypnale) in the south-west coast and Western Ghats [2]. Joseph Fayrer of the Indian Medical Service first quantified human snakebite deaths in 1869 for about half of “British India” (including modern Pakistan, Bangladesh and Burma), finding that 11,416 people had died of snakebites [3]. Subsequent estimates of human deaths from snakebite prior to Indian Independence ranged from 7,400 to 20,000 per year [4]–[6]. Government of India hospitals from all but six states reported only 1,364 snakebite deaths in 2008 [7] but this is widely believed to be an under-report as many victims of snakebite choose village-based traditional therapists and most die outside government hospitals. Community-based surveys in some localities have shown much higher annual mortality rates, ranging widely from 16.4 deaths/100,000 in West Bengal [8] to 161/100,000 in the neighbouring Nepal Terai [9]. However, such focal data cannot be extrapolated to provide national or even state totals because of the heterogeneity of snakebite incidence. These uncertainties have resulted in indirect estimates of annual snakebite mortality in India that varied from approximately 1,300 to 50,000 [6], [7], [10]–[13]. To fill this gap in knowledge, we estimated snakebite deaths directly from a large continuing study of mortality in India. Methods Ethics Statement Ethics approval for the Million Deaths Study (MDS) was obtained from the Post Graduate Institute of Medical Research, St. John's Research Institute and St. Michael's Hospital, Toronto, Ontario, Canada [14]–[15]. Most deaths in rural India take place at home without prior attention by any qualified healthcare worker, so most causes are not medically certified [14]–[15]. Other approaches are therefore needed to help determine the probable causes of such deaths. The Registrar General of India (RGI) organises the Sample Registration System (SRS), which monitors all births and deaths in a nationally representative selection of 1.1 million homes throughout all 28 states and seven union territories of India. India was divided into approximately one million areas for the 1991 census, each with about 1,000 inhabitants. In 1993, the RGI randomly selected 6,671 of these areas to be represented in the SRS. Household characteristics were recorded and then enumerated twice yearly thereafter, documenting new births and deaths, but not the causes of death [16]. Since 2002, one of 800 non-medical field staff (trained by the RGI in appropriate fieldwork methods) visited each SRS area every six months to record a written narrative (in the local language) for each death from families or other reliable informants. In addition to the narratives, answers to standard questions about the deaths were also recorded in the field report. Fieldwork quality control methods were used routinely, including random re-sampling by teams reporting directly to the study investigators [14], [15]. This survey is part of the MDS, which seeks to assign causes to all deaths in SRS areas for the period between 2001–14 [14]–[16], [17]–[19]. These field reports, or ‘verbal autopsies’, were emailed randomly (based on the language of the narrative) to at least two of 130 collaborating physicians trained in disease coding. Physicians worked independently to assess the probable underlying cause of death, assigning each case a three-character International Classification of Diseases (ICD; 10th revision) code [20]. Any differences between the two coders were resolved by anonymous reconciliation between them (asking each to reconsider) or, for persisting differences, adjudication by a third physician (3% or 15/562 of snakebite deaths, and 18% or 22,845/122,848 of all deaths). The physician coders' training and their written guidelines (available online [21]) instructed them to use their best medical judgement to determine the most probable cause of death. Field reports could not be collected on 12% of the identified deaths due to migration or change of residence. As these missing deaths were mostly random, a systematic misclassification in cause of death was unlikely. We used logistic regression to quantify the odds of snakebite versus other deaths for gender, state, religion, education, occupation, place of death and season. Risk is measured compared to the reference group of lowest risk for each variable. Climate data on rainfall and temperature were obtained for each state from the India Meteorological Department [22]–[23]. The proportion of cause specific deaths in each age category was weighted by the inverse probability of household selection within rural and urban sub divisions of each state, to account for the sampling design [16]. Using methods described earlier [14]–[15], [17]–[19], the resulting proportion of deaths from each cause was applied to the United Nations (UN) population division estimates of deaths in India in 2005 [24] (9.8 million, upper and lower limits 9.4–10.3 million) to generate cause- specific death totals and rates. The UN totals (which undergo independent demographic review [24]) were used because the SRS underestimates adult mortality rates by about 10% [25]–[26]. The UN totals are not affected by the 12% of the SRS-enumerated deaths that were unavailable for interview in our survey. Totals for 2005 were used because they: (i) were most complete; (ii) could be compared to the available Indian Census projections for 2006; and (iii) captured information prior to the implementation of a new national health program in rural areas [27]. However, applying the 2001–03 proportions to the 2005 total deaths did not introduce major biases since there was little change in the yearly distribution in snakebite deaths in our survey, or in the annual number of deaths reported from snakebites in routine national hospital surveillance data between 2003 and 2008 [7]. Results Snakebite deaths in study and nationally Of the 643 deaths coded by physicians as ICD-10 codes X20–X29 (contact with venomous animals and plants), 523 (81%) were coded as X20 (venomous snakes) and review of these yielded no misclassified causes. Central re-examination of the symptoms and key words found 39 of 45 deaths coded as X27 (animals) and X29 (uncertain) to be snakebite deaths. We excluded 75 deaths coded as X21–X25 (various arthropods), X26 (marine organisms) and X28 (plants). Among all 122,848 deaths, 2,179 of the deaths that were randomly chosen to be re-interviewed by independent teams were eventually matched to the identical houses and individuals of the MDS. Of the 2,179 re-sampled deaths, 9 were coded as snakebites, and 7 of these were found in the MDS. Thus, the sensitivity and specificity of the SRS field survey, assuming the re-sample deaths are the standard comparison, was 78% (7/9) and 100% (2,170/2,170), respectively. A total of 562 of the 122,848 deaths (0.47% weighted by sampling probability or 0.46% unweighted) were from snakebites (Table 1). Almost all snakebite deaths (544 or 97%) were in rural areas. More men (330, 59%) than women (232, 41%) died from snakebites (overall ratio of 1.4 to 1). The proportion of all deaths from snakebites was highest at ages 5–14 years. Only 23% (127/562) of the deaths occurred in a hospital or other healthcare facility. 10.1371/journal.pntd.0001018.t001 Table 1 Snakebite deaths in the present study, 2001–03 and estimated national totals, by age. Study deaths 2001–03 All India estimates 2005 Numbers attributed Proportion snakebite deaths per 1,000* Died in health facility Rural area All causes deaths/population (million): UN estimates † Snakebite deaths in thousands Death rate per 100,000 Age in years Male/Female Snakebite/all causes National Rural 0–4 29/23 52/23,630 2.1 8 52 2.3/128 5.0 3.9 4.9 5–14 73/41 114/3,881 28.5 24 111 0.3/246 9.7 4.0 5.1 15–29 80/62 142/9,121 15.9 31 134 0.7/313 11.0 3.5 4.7 30–44 60/44 104/10,872 9.4 30 102 0.9/222 8.3 3.8 5.3 45–59 52/27 79/18,133 4.6 22 73 1.5/142 6.8 4.8 6.2 60–69 21/24 45/21,136 2.2 6 44 1.5/49 3.3 6.6 8.7 70+ 15/11 26/36,075 0.7 6 28 2.6/30 1.8 6.2 8.0 All ages 330/232 562/122,848 4.7 127 (23%) 544 (97%) 9.8/1,130 45.9 4.1 5.4 (99% CI ) (40.9, 50.9) (3.6, 4.5) (4.8,6.0) The overall study death total of 122,848 includes 8.7% senility, unspecified or ill defined deaths, which were not assigned to any specific disease categories. *Proportional snakebite mortality per 1,000 after applying sample weights to adjust urban-rural probability of selection. †: United Nations 2005 estimates for India. Expressed as national totals, snakebites caused 45,900 deaths in India in 2005 (99% CI 40,900 to 50,900). The age-standardised death rate per 100,000 population per year was 4.1 (99% CI 3.6–4.5) nationally and was 5.4 (99% CI 4.8–6.0) in rural areas. Risk factors and seasonality Figure 1 shows the odds ratios for snakebite deaths versus other deaths, adjusted for age, gender, and for high prevalence states (13 states with age-standardised snakebite death rates greater than 3 per 100,000) versus other states. The risks of snakebite deaths were significantly increased among Hindus and farmers/labourers, deaths occurring outside home, and during the monsoon months of June to September (Figures 1 and 2). In contrast, gender and education were not significantly associated with risk of snakebite death. About 5,000–7,000 snakebite deaths per month occurred during the monsoon period, compared to less than 2,000 deaths in the winter months. Monthly numbers of snakebite deaths correlated with rainfall (R = 0.93, p<.0001) and mean minimum temperature (R = 0.80, p = 0.0017), but not with mean maximum temperature (R = 0.35, p = 0.2585; Figure 2). 10.1371/journal.pntd.0001018.g001 Figure 1 Selected risk factors for snakebite mortality in India (study deaths 2001–03). Odds ratio after adjusting for age, gender and states with a high prevalence of snakebite deaths (see definition in Table 2). Occupation ‘Other’ includes students and house wives. 10.1371/journal.pntd.0001018.g002 Figure 2 Seasonality pattern of snakebite mortality and rainfall in states with high prevalence of snakebite deaths (2001–03). Rainfall amount (mm) is cumulative daily rainfall for the past 24 hours measured by the India Meteorological Department [22], [23]. Maximum and minimum temperatures are also measured daily and presented as monthly averages across the 13 snakebite high prevalence states. Pearson correlation coefficients between snakebite mortality and weather were: (i) rainfall; 0.93 (p<0.0001); (ii) minimum temperature: 0.80 (p = 0.0017); (iii) maximum temperature: 0.35 (p = 0.2585). State mortality patterns Annual age-standardised mortality rates per 100,000 from snakebite varied between states, from 3.0 (Maharashtra) to 6.2 (Andhra Pradesh) in the 13 states with highest prevalence (average 4.5) compared to 1.8 in the rest of the country (Table 2; Figure 3). Total deaths were highest in Uttar Pradesh (8,700), Andhra Pradesh (5,200), and Bihar (4,500). The age and gender of snakebite deaths also varied by region, although these differences were not significant due to the small numbers of snakebite deaths in each state. Deaths at ages 5–14 years were prominent in the states of Jharkhand and Orissa, whereas deaths at older ages were prominent in Andhra Pradesh, Bihar, Madhya Pradesh, and Uttar Pradesh (data not shown). In Bihar, Madhya Pradesh, Maharashtra and Uttar Pradesh, female deaths exceeded male deaths (Table 2). 10.1371/journal.pntd.0001018.g003 Figure 3 Estimated deaths and standardized death rates in states with high prevalence of snakebite deaths, 2005. Death rates are standardised to 2005 UN population estimates for India [24]. The vertical bars represent the state wise estimated deaths (in thousands). Total snakebite deaths for the 13 states with high-prevalence of snakebite death are 42,800 or 93% of the national total (these states have about 85% of the total estimated population of India). States where the snakebite death rate was below 3/100,000 or where populations are less than 10 million are not shown. The states with high-prevalence of snakebite deaths are: AP-Andhra Pradesh, BR-Bihar, CG-Chhattisgarh, GJ-Gujarat, JH-Jharkhand, KA-Karnataka, MP Madhya Pradesh, MH-Maharashtra, OR-Orissa, RJ- Rajasthan, TN-Tamil Nadu, UP-Uttar Pradesh, WB-West Bengal. 10.1371/journal.pntd.0001018.t002 Table 2 Estimated snakebite deaths in the Indian states with a high prevalence of snakebite deaths, 2005. Study deaths 2001–03 Estimated state and national deaths 2005 State Snakebite/all causes Male/female Died outside health facility Proportional mortality/1,000 Snakebites deaths in thousands Death rate per 100,000 States with high-prevalence of snakebite deaths * Andhra Pradesh 45/5,831 31/14 42 7.4 5.2 6.2 Madhya Pradesh 41/7,257 20/21 31 5.7 4.0 5.9 Orissa 37/7,364 22/15 26 5.2 2.2 5.6 Jharkhand 12/2,179 8/4 12 5.8 1.5 4.9 Bihar 50/9,824 21/29 45 5.8 4.5 4.9 Tamil Nadu 38/6,316 26/12 28 5.1 3.1 4.7 Uttar Pradesh 78/15,403 36/42 72 4.8 8.7 4.6 Chhattisgarh 13/2,328 6/7 11 4.6 1.0 4.4 Karnataka 41/6,961 32/9 32 5.0 2.4 4.2 West Bengal 40/8,330 24/16 20 4.7 3.0 3.5 Gujarat 28/6,151 20/8 20 4.1 1.9 3.5 Rajasthan 29/6,769 18/11 24 4.2 2.1 3.3 Maharashtra 28/6,274 9/19 18 3.9 3.2 3.0 Sub total 480/90,987 273/207 381 5.1 42.8 4.5 Remaining states 82/31,861 57/25 54 2.2 3.1 1.8 All India 562/122,848 330/232 435 4.7 45.9 4.1 (99% CI) (40.9, 50.9) (3.6, 4.5) States are listed in descending order of death rates. Death rates are standardised to 2005 UN national estimates for India. *States with a high-prevalence of snakebite deaths are defined as those with more than 10 million people where the annual snakebite death rate exceeds 3 per 100,000 population. Discussion Snakebite remains an important cause of accidental death in modern India, and its public health importance has been systematically underestimated. The estimated total of 45,900 (95% CI 40,900–50,900) national snakebite deaths in 2005 constitutes about 5% of all injury deaths and nearly 0.5% of all deaths in India. It is more than 30-fold higher than the number declared from official hospital returns [7]. The underreporting of snake bite deaths has a number of possible causes. Most importantly, it is well known that many patients are treated and die outside health facilities – especially in rural areas. Thus rural diseases, be they acute fever deaths from malaria and other infections [19] or bites from snakes or mammals (rabies; [28]), are underestimated by routine hospital data. Moreover, even hospital deaths may be missed or not reported as official government returns vary in their reliability, as shown from a study of snakebites in Sri Lanka [29]. The true burden of mortality from snakebite revealed by our study is similar in magnitude to that of some higher profile infectious diseases; for example, there is one snakebite death for every two AIDS deaths in India [18]. Consequently, snakebite control programmes should be prioritised to a level commensurate with this burden. Our data suggest underestimation in recent global estimates of mortality from snakebite deaths [10]: the upper bounds of recent annual estimates were 94,000 deaths globally and 15,000 deaths in India. This total for India is only about one-third of the snake bite deaths detected in our study. The incidence of snakebite deaths per 100,000 population per year in a recent community-based study in Bangladesh was similar to ours [30], suggesting that much of South Asia might have thousands more snakebite deaths than is currently assumed. Considering the widely accepted gross underestimation of snakebite deaths in Africa [11], it seems highly probable that well over 100,000 people die of snakebite in the world each year. A minimal number of non-fatal snakebites in India may be estimated with far less certainty. Indian data from routine public sector hospitals [7] are clearly under-reports of deaths (recording only 1 in 5 of the deaths we estimated to have occurred in hospital). Nonetheless, the ratio of non-fatal bites (about 140,000) to fatal bites (about 2,200) in these hospital data from 2003–08 (about 64∶1) is informative of the relative burden of bites to deaths. Very crudely, even if we halve the fatal/nonfatal bite ratio to 32, this would suggest at least 1.4 million non-fatal bites corresponding to the 45,000 fatal bites. The actual number of non-fatal bites in India may well be far higher, as the community-based study in Bangladesh found about 100 non-fatal bites for each death [30]. Our study has limitations; notably the misclassification of snakebite deaths. However, snakebites are dramatic, distinctive and memorable events for the victim's family and neighbours, making them more easily recognizable by verbal autopsy. We observed a reasonably high sensitivity and specificity when compared to re-sampled deaths. Confusion with arthropod bites and stings is unlikely because of the different circumstances, size and behaviour of the causative animal and the course of envenoming. For example, most deaths from hymenoptera stings result from rapidly evolving anaphylaxis. Kraits (important agents of snakebite death in South Asia) may unobtrusively envenom sleeping victims, who may die after developing severe abdominal pain, descending paralysis, respiratory failure and convulsions [31]. Such deaths might not be associated with snakebite at all. These examples suggest possible underestimation of deaths in our data. Since the numbers of deaths observed in each state were small, the estimated totals for each state are uncertain. However, the state distribution is broadly consistent with that reported by the RGI survey of deaths in selected rural areas in the 1990s [32]. The marked geographic variation across states in our study is similar to that in a country-wide survey conducted during the period 1941–45, which identified Bengal, Bihar, Tamil Nadu, Uttar Pradesh, Madhya Pradesh, Maharashtra and Orissa as having the highest death rates from snakebite [6]. Moreover, despite the obvious underestimates in hospitalised data [7], their geographical distribution of bites and deaths were similar to what we observed from household reports of deaths. The marked differences in snakebite mortality between states of India may be attributable to variations in human, snake and prey populations, and in local attitudes [8] and health services. The 13 states with the highest snakebite mortality are inhabited by the four most common deadly venomous snakes: Naja naja, Bungarus caeruleus, Echis carinatus and Daboia russelii. With the exception of E. carinatus, which favours open wasteland, these are widely distributed species of the plains and low hills where most Indians live. While some species can inhabit altitudes of up to 2,700 metres [2], this is exceptional and higher mountainous regions have considerably lower death rates. As found in an earlier study [33], the peak age group of snakebite deaths is 15–29 years (25% or 142/562). However, the relative risk of dying from snakebite versus another cause was greater at ages 5–14 years. The peak age range and gender associated with snakebite mortality varied between states, perhaps reflecting differences in the relative numbers of children and women involved in agricultural work [34]–[35]. The slight excess among Hindus may reflect more tolerance of snakes and greater use of traditional treatments [2]. Snakebites and snakebite fatalities peak during the monsoon season in India [33], [36] and worldwide [10], probably reflecting agricultural activity, flooding, increased snake activity, and abundance of their natural prey. Only 23% of the snakebite deaths identified in our survey occurred in hospital, consistent with an earlier study from five states [33]. This emphasises three points: (i) hospital-based data reflect poorly the national burden of fatal snakebites; (ii) inadequacy of current treatment of snakebite in India; and (iii) vulnerability of snakebite victims outside hospital. Practicable solutions include strengthening surveillance to allow a more accurate perception of the magnitude of the problem, improving community education to reduce the incidence of snakebites and speed up the transfer of bitten patients to medical care, improving the training of medical staff at all levels of the health service (including implementation of the new WHO guidelines [12]), and deployment of appropriate antivenoms and other interventional tools where they are needed in rural health facilities to decrease case fatality [36]–[38]. In addition, phylogenetic and venom studies are needed to ensure appropriate design of antivenoms to cover the species responsible for serious envenoming.
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The Feasibility of Canine Rabies Elimination in Africa: Dispelling Doubts with Data
Tiziana Lembo, Katie Hampson, Magai T Kaare … (2010)
Introduction Rabies is a viral zoonosis caused by negative-stranded RNA viruses from the Lyssavirus genus. Genetic variants of the genotype 1 Lyssavirus (the cause of classical rabies) are maintained in different parts of the world by different reservoir hosts within ‘host-adaptive landscapes’ [1]. Although rabies can infect and be transmitted by a wide range of mammals, reservoirs comprise only mammalian species within the Orders Carnivora (e.g. dogs, raccoons, skunks, foxes, jackals) and Chiroptera (bats). From the perspective of human rabies, the vast majority of human cases (>90%) result from the bites of rabid domestic dogs [2] and occur in regions where domestic dogs are the principal maintenance host [3]. Over the past three decades, there have been marked differences in efforts to control canine rabies. Recent successes have been demonstrated in many parts of central and South America, where canine rabies has been brought under control through large-scale, synchronized mass dog vaccination campaigns [4]. As a result, not only has dog rabies declined, but human rabies deaths have also been eliminated, or cases remain highly localized [5]. The contrast with the situation in Africa and Asia is striking; here, the incidence of dog rabies and human rabies deaths continue to escalate, and new outbreaks have been occurring in areas previously free of the disease (e.g. the islands of Flores and Bali in Indonesia – [6]; http://wwwn.cdc.gov/travel/contentRabiesBaliIndonesia2008.aspx). In this paper, we identify four major reasons commonly given for the lack of effective domestic dog rabies control including (1) low prioritisation, (2) epidemiological constraints, (3) operational constraints and (4) lack of resources (Table 1), focussing on the situation in Africa. We address each of these issues in turn, using outputs from modelling approaches and data from field studies to demonstrate that there are no insurmountable logistic, practical, epidemiological, ecological or economic obstacles. As a result, we conclude that the elimination of canine rabies is a feasible objective for much of Africa and there should be no reasons for further delay in preventing the unnecessary tragedy of human rabies deaths. 10.1371/journal.pntd.0000626.t001 Table 1 Reasons commonly given for the lack of effective dog rabies control. Reason Explanation Oral evidence Published evidence LOW PRIORITISATION Lack of accurate data on the disease burden and low recognition among public health practitioners and policy makers; lack of inclusion of rabies in global surveys of disease burden; only recent recognition of rabies as a neglected tropical disease; statements of rabies as an ‘insignificant human disease’ Ministries of Health; statements by doctors and health workers; WHO (up until 2007) I-VI* EPIDEMIOLOGICAL CONSTRAINTS Abundance of wild animals and uncertainties about the required levels of vaccination coverage SEARG meetings, scientific meetings, national veterinary meetings; statements from district veterinary officers and local communities; draft rabies control policies VII-XIX OPERATIONAL CONSTRAINTS Perception of existence of many inaccessible stray/ownerless dogs SEARG meetings, inter-ministerial meetings, national veterinary meetings; statements from district veterinary and medical officers, and livestock officers; draft rabies control policies; international organizations XX-XXVIII Owners unwilling or unable to bring dogs for vaccination SEARG meetings, inter-ministerial meetings, national veterinary meetings, scientific meetings; statements by veterinary and livestock officers XXIX,XXX Insufficient knowledge of dog population size and ecology SEARG meetings, inter-ministerial meetings, scientific meetings; statements from veterinary and livestock officers and wildlife authorities; draft rabies control policies; international organizations XIV,XXIV,XXXI LACK OF RESOURCES Weak surveillance and diagnostic capacity SEARG meetings, inter-ministerial meetings; international and national reference laboratories; international organizations VI,XXIII,XXIV,XXXII-XXXVIII Insufficient resources available to veterinary services SEARG meetings, inter-ministerial meetings, scientific meetings, national veterinary meetings; statements from politicians, veterinary authorities, local communities, wildlife authorities; international organizations; media XXVI,XXXIV,XXXVII,XXXIX,XL-XLIII SEARG = Southern and Eastern Africa Rabies Group. *Including indirect evidence (e.g. absence of any mention of rabies in published literature indicating lack of priority). See Appendix S1 for references. Methods This paper compiles previously published data (see references below) and additional analyses of those data, but we present a brief summary of the data collection methods below. Hospital records of animal-bite injuries compiled from northwest Tanzania were used as primary data sources. These data informed a probability decision tree model for a national disease burden evaluation [7], which has since been adapted for global estimates of human rabies deaths and Disability-Adjusted Life Years (DALYs) lost due to rabies [3], a standardized measure for assessing disease burden [8],[9]. Hospital records were also used to initiate contact tracing studies [10]–[12], whereby bite-victims were interviewed to obtain more detail on the source and severity of exposure and actions taken, allowing subsequent interviews with other affected individuals (not documented in hospital records) including owners of implicated animals. Statistical techniques applied to these data for estimating epidemiological parameters and inferring transmission links are described elsewhere [10],[12]. Rabies monitoring operations including passive and active surveillance involving veterinarians, village livestock field officers, paravets, rangers and scientists were used to collect samples from carcasses (domestic dogs and wildlife whenever found), which were subsequently tested and viral isolates were sequenced [10], [13]–[16], with results being used to inform estimates of rabies-recognition probabilities [7] and for phylogenetic analyses [10],[16]. Operational research on domestic dog vaccination strategies was carried out in a variety of settings [14],[17]. Household interviews were also used for socio-economic surveys and to evaluate human:domestic dog ratios, levels of vaccination coverage achieved and reasons for not bringing animals to vaccination stations [17],[18]. The study was approved by the Tanzania Commission for Science and Technology with ethical review from the National Institute for Medical Research (NIMR). This retrospective study involved collection of interview data only, without clinical intervention or sampling, therefore we considered that informed verbal consent was appropriate and this was approved by NIMR. Permission to conduct interviews was obtained from district officials, village and sub-village leaders in all study locations. At each household visited, the head of the household was informed about the purpose of the study and interviews were conducted with verbal consent from both the head of the household and the bite victim (documented in a spreadsheet). Approval for animal work was obtained from the Institutional Animal Care and Use Committee (IACUC permit #0107A04903). Results/Discussion (a) There is not enough evidence to define rabies control as a priority A principal factor contributing to a low prioritization of rabies control has been the lack of information about the burden and impact of the disease [19],[20]. Data on human rabies deaths, submitted from Ministries of Health to the World Health Organization (WHO), are published in the annual World Surveys of Rabies and through the WHO Rabnet site (www.who.int/rabies/rabnet/en). For the WHO African region (AFRO) comprising 37 countries, these surveys report an average of 162 human deaths per year between 1988 and 2006. It is therefore unsurprising that for national and international policy-makers, rabies pails into insignificance in comparison with other major disease problems. This perceived lack of significance of human rabies is reflected in the absence of any mention of rabies in either of the two published Global Burden of Disease Surveys [21],[22], which assessed more than 100 major diseases. These surveys adopted the metric of the DALY which is widely used as the principal tool for providing consistent, comparative information on disease burden for policy-making. Until recently no estimates of the DALY burden were available for rabies. Official data on human rabies deaths submitted to WHO from Africa are widely recognized to greatly under-estimate the true incidence of disease. The reasons for this are manifold: (1) rabies victims are often too ill to travel to hospital or die before arrival, (2) families recognize the futility of medical treatment for rabies, (3) patients are considered to be the victims of bewitchment rather than disease, (4) clinically recognized cases at hospitals may go unreported to central authorities, and (5) misdiagnosis is not uncommon. The problems of misdiagnosis were highlighted by a study of childhood encephalitis in Malawi, in which 3/26 (11.5%) cases initially diagnosed as cerebral malaria were confirmed as rabies through post-mortem tests [23]. Several recent studies have contributed information that consistently demonstrates that the burden of canine rabies is not insubstantial. Human rabies deaths Estimates of human rabies cases from modeling approaches, using the incidence of dog-bite injuries and availability of rabies post-exposure prophylaxis (PEP), indicate that incidence in Africa is about 100 times higher than officially reported, with ∼24,000 deaths in Africa each year [3],[7]. Consistent figures have subsequently been generated from detailed contact-tracing data: in rural Tanzanian communities with sporadic availability of PEP (a typical scenario in developing countries), human rabies deaths occur at an incidence of ∼1–5 cases/100,000/year (equivalent to 380–1,900 deaths per year for Tanzania) [11]. Similarly, a multi-centric study from India reported 18,500 human rabies deaths per year [24], consistent with model outputs of 19,700 deaths for India [3]. A crude comparison of annual human deaths for a range of zoonotic diseases is shown in Figure 1 (top). While diseases such as Severe Acute Respiratory Syndrome (SARS), Rift Valley Fever and highly pathogenic avian influenza cause major concerns as a result of pandemic potential and economic losses, these figures provide a salutary reminder of the recurrent annual mortality of rabies and other neglected zoonoses, such as leishmaniasis and Human African Trypanosomiasis (HAT). Decision-tree models applied to data from East Africa and globally indicate that the DALY burden for rabies exceeds that of most other neglected zoonotic diseases (Figure 1 - bottom) [3],[25],[26]. 10.1371/journal.pntd.0000626.g001 Figure 1 Annual human deaths for a range of zoonoses and global disability-adjusted life years (DALYs) scores for neglected zoonoses. Top figure - Numbers of human deaths per year for rabies compared with peak annual deaths from selected epidemic zoonoses (Severe Acute Respiratory Syndrome, SARS, 2003; H5N1, 2006; Nipah, 1999; and Rift Valley Fever 2007). Data sources: Rabies (LVII), Leishmaniasis, Human African Trypanosomiasis (HAT), Chagas Disease and Japanese Encephalitis (LVIII), SARS (LIX), Influenza A H5N1 (LX), Nipah (LXI), Rift Valley Fever (LXII,LXIII). See Appendix S1 for references. Bottom figure - Global DALY scores for neglected tropical diseases reported in LXIV and LVII and also assuming no post-exposure treatment (dark grey). See Appendix S1 for references. Human animal-bite injuries and morbidity Most of the rabies DALY burden is attributed to deaths, rather than morbidity because of the short duration of clinical disease. The DALY burden for rabies is particularly high, because most deaths occur in children and therefore a greater number of years of life are lost [25],[27]. DALY estimates incorporate non-rabies mortality and morbidity in terms of adverse reactions to nerve-tissue vaccines (NTVs) [3], which are still widely used in some developing countries such as Ethiopia, however rabies also causes substantial ‘morbidity’ as a direct result of injuries inflicted by rabid animals, and this is not included in DALY estimates. Contact-tracing studies suggest an incidence as high as 140/100,000 bites by suspected rabid animals in rural communities of Tanzania [11]. Thus, for every human rabies death there are typically more than ten other rabid animal-bite victims who do not develop signs of rabies, because they obtain PEP (Figure 1 - bottom) or are simply fortunate to remain healthy. The severity of wounds has not yet been quantified, but case-history interviews suggest that injuries often involve multiple, penetrating wounds that require medical treatment. Economic burden The major component of the economic burden of rabies relates to high costs of PEP, which impacts both government and household budgets. With the phasing out of NTVs, many countries spend millions of dollars importing supplies of tissue-culture vaccine (∼$196 million USD pa [3]). At the household level, costs of PEP arise directly from anti-rabies vaccines and from high indirect (patient-borne) costs associated with travel (particularly given the requirement of multiple hospital visits), medical fees and income loss [3],[28]. Indirect losses, represent >50% of total costs (Figure 2). Total costs have been estimated conservatively at $40 US per treatment in Africa and $49 US in Asia accounting respectively for 5.8% and 3.9% of annual per capita gross national income [3]. Poor households face difficulties raising funds which results in considerable financial hardship and substantial delays in PEP delivery [11],[28]. Shortages of PEP, which are frequent in much of Africa, further increase costs as bite victims are forced to travel to multiple centres to obtain treatment, also resulting in risky delays [11]. 10.1371/journal.pntd.0000626.g002 Figure 2 Economic burden of canine rabies (data source: LVII in Appendix S1). PET, Post-exposure treatment. Additional economic losses relate to livestock losses derived from an incidence of 5 deaths/100,000 cattle estimated to cost $12.3 million annually in Africa and Asia [3]. However, substantially higher incidence has been recorded in Tanzania, with 12–25 cases/100,000 cattle reported annually in rural communities (Hampson, unpublished). Canine rabies introduced from sympatric domestic dog populations is also recognized as a major threat to endangered African wild dogs (Lycaon pictus) and Ethiopian wolves (Canis simensis) [29]–[32]. Potential losses of tourism revenue may be substantial; African wild dogs are a major attraction in South Africa National Parks with the value of a single pack estimated at $9,000 per year [33] and Ethiopian wolves are a flagship species for the Bale Mountains National Park. Psychological impact An important, but often under-appreciated component of disease burden is the psychological impact on bite-victims and their families. In rural Tanzania, >87% of households with dog bite victims feared a bite from a suspected rabid animal more than malaria [28] because malaria can be treated whereas clinical rabies is invariably fatal and malaria treatment is generally affordable and available locally in comparison to PEP. When human rabies cases occur, the horrifying symptoms and invariably fatal outcome result in substantial trauma for families, communities and health care workers [34]. (b) Epidemiological constraints Increasing incidence of rabies in Africa has prompted concerns that the epidemiology of the disease may be more complex, involving abundant wildlife carnivores that may sustain infection cycles [13], [35]–[38]. There is also uncertainty about the level of vaccination coverage needed to control rabies particularly in rapidly growing domestic dog populations [39],[40]. To eliminate infection, disease control efforts need to be targeted at the maintenance population [41]. This is clearly demonstrated for fox rabies in Western Europe, whereby control of rabies in foxes (through mass oral vaccination) has led to the disappearance of rabies from all other ‘spill-over’ hosts [42]. Despite the predominance of domestic dog rabies in Africa, the role of wildlife as independent maintenance hosts has been debated, and many perceive the abundance of wildlife as a barrier to elimination of canine rabies on the continent. It has also been argued that the predominance of dog rabies is an artefact of poor surveillance and under-reporting in wildlife populations [43]. In the wildlife-rich Serengeti ecosystem in Tanzania, evidence suggests that domestic dogs are the only population essential for maintenance [10],[13],[16]: (1) phylogenetic data showed only a single southern Africa canid-associated variant (Africa 1b) circulating among different hosts [16]; (2) transmission networks suggested that, for wildlife hosts, within-species transmission cannot be sustained [16]; and (3) statistical inference indicated that cross-species transmission events from domestic dogs resulted in only relatively short-lived chains of transmission in wildlife with no evidence for persistence [10]. The conclusion that domestic dogs are the only maintenance population in such a species-rich community suggests that elimination of canine rabies through domestic dog vaccination is a realistic possibility, and provides grounds for optimism for wider-scale elimination efforts in Africa. In other parts of central and west Africa, transmission of rabies appears to be driven by domestic dogs [44]. An outstanding question relates to southern Africa. Earlier and recent evidence indicate that jackal species (Canis mesomelas and C. adustus) and bat-eared foxes (Otocyon megalotis) may maintain the canid variant in specific geographic loci in South Africa and Zimbabwe [2], [36]–[38], [45]–[50], but it is still not clear whether these cycles can be sustained over large spatial and temporal scales in the absence of dog rabies [13],[51],[52]. Independent wildlife cycles may preclude continent-wide elimination of this variant through dog vaccination alone and wildlife rabies control strategies, in conjunction with dog vaccination, may need to be considered in specific locations [38]. A critical proportion of the population must be protected (Pcrit) to eliminate infection and this threshold can be calculated from the basic reproductive number (R0, defined as the average number of secondary infections caused by an infected individual in a susceptible population) [53]. Vaccinating a large enough proportion of the population to exceed Pcrit will not only protect the vaccinated individuals but will reduce transmission such that, on average, less than one secondary infection will result from each primary case (effective reproductive number, Re 80% coverages can still be achieved through house-to-house delivery strategies or community-based animal health workers [17]. Young pups usually make up a large proportion (>30%) of African dog populations [62] and there is a widespread perception among veterinary authorities and dog owners that they should not be vaccinated, which leads to insufficient coverage [17]. However, rabies vaccines can safely be administered to pups 0.5 IU/ml) of rabies virus neutralizing antibody [64]. The issue of inclusion of pups can effectively be addressed through appropriate advertising before campaigns. Cost-recovery, through charging dog owners for rabies vaccination, is widely promoted for sustainable programmes and to encourage responsible dog ownership. However, charging for a vaccination that represents a public rather than a private good, can be counterproductive, resulting in low turnouts and coverage ( 600,000 PEP courses per year at an estimated cost of ∼$27 million/year [84]. Although domestic dog populations need to be targeted for the effective control of rabies, this is usually deemed to be the responsibility of veterinary services even though many of the benefits accrue to the medical sector. In rural Tanzania, dog vaccination campaigns led to a rapid and dramatic decline in demand for costly human PEP [14]. In pastoral communities, vaccination not only reduced rabies incidence, but has now resulted in a complete absence of exposures reported in local hospitals for over two years (Figure 4). 10.1371/journal.pntd.0000626.g004 Figure 4 Number of cases of bite injuries reported to hospitals in pastoralist communities to the east of Serengeti National Park (north-western Tanzania). Numbers are recorded as a result of bites from both rabid and normal healthy animals as well as those of unknown status (either the bite victims could not be traced, or insufficient information could be obtained during interviews to make an informed judgement about the health of the biting animal). The arrows mark the end of successive dog vaccination campaigns. Large-scale campaigns can therefore translate into human lives and economic savings through reduced demand for PEP. Costs per dog vaccinated are generally estimated to be low (rural Tanzania ∼$1.73 [17], Philippines ∼$1.19–4.27 [85], Tunisia ∼$1.3 [86], Thailand ∼$1.3 [86] and Urban Chad ∼$1.8 [87]) and preliminary studies suggest that including dog vaccination in human rabies prevention strategies would be a highly cost-effective intervention at ∼US $25/DALY averted (S. Cleaveland, unpublished data; see also 82). Developing joint financing schemes for rabies prevention and control across medical and veterinary sectors would provide a mechanism to use savings in human PEP to sustain rabies control programs in domestic dogs. Although conceptually simple, the integration of budgets across different Ministries is likely to pose political and administrative challenges. However, given sufficient political will and commitment, developing sustained programmes of dog vaccination that result in canine rabies elimination should be possible. In conclusion, here we show that a substantial body of epidemiological data have now been gathered through multiple studies demonstrating that: (1) rabies is an important disease that exerts a substantial burden on human and animal health, local and national economies and wildlife conservation, (2) domestic dogs are the sole population responsible for rabies maintenance and main source of infection for humans throughout most of Africa and Asia and therefore control of dog rabies should eliminate the disease, (3) elimination of rabies through domestic dog vaccination is epidemiologically feasible, (4) the vast majority of domestic dog populations across sub-Saharan Africa are accessible for vaccination and the few remaining factors compromising coverage can be addressed by engaging communities through education and awareness programs, (5) new diagnostic and surveillance approaches will help evaluate the impact of interventions and focus efforts towards elimination, and (6) dog rabies control is affordable, but is likely to require intersectoral approaches for sustainable programmes that will be needed to establish rabies-free areas. Supporting Information Appendix S1 Appendix with additional references. (0.07 MB DOC) Click here for additional data file.
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Causes of neonatal and child mortality in India: a nationally representative mortality survey.
Shaun Morris, Sandra Black, Prabhat Jha … (2010)
More than 2·3 million children died in India in 2005; however, the major causes of death have not been measured in the country. We investigated the causes of neonatal and child mortality in India and their differences by sex and region. The Registrar General of India surveyed all deaths occurring in 2001-03 in 1·1 million nationally representative homes. Field staff interviewed household members and completed standard questions about events that preceded the death. Two of 130 physicians then independently assigned a cause to each death. Cause-specific mortality rates for 2005 were calculated nationally and for the six regions by combining the recorded proportions for each cause in the neonatal deaths and deaths at ages 1-59 months in the study with population and death totals from the United Nations. There were 10,892 deaths in neonates and 12,260 in children aged 1-59 months in the study. When these details were projected nationally, three causes accounted for 78% (0·79 million of 1·01 million) of all neonatal deaths: prematurity and low birthweight (0·33 million, 99% CI 0·31 million to 0·35 million), neonatal infections (0·27 million, 0·25 million to 0·29 million), and birth asphyxia and birth trauma (0·19 million, 0·18 million to 0·21 million). Two causes accounted for 50% (0·67 million of 1·34 million) of all deaths at 1-59 months: pneumonia (0·37 million, 0·35 million to 0·39 million) and diarrhoeal diseases (0·30 million, 0·28 million to 0·32 million). In children aged 1-59 months, girls in central India had a five-times higher mortality rate (per 1000 livebirths) from pneumonia (20·9, 19·4-22·6) than did boys in south India (4·1, 3·0-5·6) and four-times higher mortality rate from diarrhoeal disease (17·7, 16·2-19·3) than did boys in west India (4·1, 3·0-5·5). Five avoidable causes accounted for nearly 1·5 million child deaths in India in 2005, with substantial differences between regions and sexes. Expanded neonatal and intrapartum care, case management of diarrhoea and pneumonia, and addition of new vaccines to immunisation programmes could substantially reduce child deaths in India. US National Institutes of Health, International Development Research Centre, Canadian Institutes of Health Research, Li Ka Shing Knowledge Institute, and US Fund for UNICEF. Copyright © 2010 Elsevier Ltd. All rights reserved.
Author and article information
Contributors
Jakob Zinsstag: Role: Editor
Journal
Journal ID (nlm-ta): PLoS Negl Trop Dis
Journal ID (iso-abbrev): PLoS Negl Trop Dis
Journal ID (publisher-id): plos
Journal ID (pmc): plosntds
Title:
PLoS Neglected Tropical Diseases
Publisher:
Public Library of Science
(San Francisco, USA
)
ISSN
(Print):
1935-2727
ISSN
(Electronic):
1935-2735
Publication date Collection:
October
2012
Publication date
(Electronic):
4
October
2012
Volume: 6
Issue: 10
Electronic Location Identifier: e1847
Affiliations
[1
]Centre for Global Health Research (CGHR), Li
Ka Shing Knowledge Institute, St. Michael's Hospital and Dalla Lana School
of Public Health, University of Toronto, Toronto, Canada
[2
]Division of Infectious Diseases, Hospital for
Sick Children, University of Toronto, Toronto, Ontario, Canada
[3
]School of Public Health, Post Graduate
Institute of Medical Research and Education, Chandigarh, India
Author notes
* E-mail:
jhap@
123456smh.ca
Article
Publisher ID: PNTD-D-12-00154DOI: 10.1371/journal.pntd.0001847
PMC ID: 3464588
PubMed ID: 23056661
SO-VID: 2dd88bd5-209e-4792-bbde-b4ea4e1b2acd
Copyright statement:
Copyright @
2012
License:
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.
History
Date
received
: 27
January
2012
Date
accepted
: 20
August
2012
Page count
Pages: 9
Funding
This study is supported by grants from the John E. Fogarty
International Center of the National Institutes of Health (R01-TW05991–01
and TW07939-01) as well as the Canada Research chair program and University of
Toronto (to Prof Jha). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the
manuscript.
Categories
Subject:
Research Article
Subject:
Biology
Subject:
Medicine
Subject:
Science Policy
Subject:
Social and Behavioral Sciences
Subject:
Veterinary Science
ScienceOpen disciplines: Infectious disease & Microbiology
Data availability:
ScienceOpen disciplines: Infectious disease & Microbiology