Conceived and designed the experiments: KH MK. Performed the experiments: KH MK MM ES. Analyzed the data: KH MK. Wrote the paper: KH APD MK JD SC.
The authors have declared that no competing interests exist.
Thousands of human deaths from rabies occur annually despite the availability of effective vaccines following exposure, and for disease control in the animal reservoir. Our aim was to assess risk factors associated with exposure and to determine why human deaths from endemic canine rabies still occur.
Contact tracing was used to gather data on rabies exposures, post-exposure prophylaxis (PEP) delivered and deaths in two rural districts in northwestern Tanzania from 2002 to 2006. Data on risk factors and the propensity to seek and complete courses of PEP was collected using questionnaires. Exposures varied from 6–141/100,000 per year. Risk of exposure to rabies was greater in an area with agropastoralist communities (and larger domestic dog populations) than an area with pastoralist communities. Children were at greater risk than adults of being exposed to rabies and of developing clinical signs. PEP dramatically reduced the risk of developing rabies (odds ratio [OR] 17.33, 95% confidence interval [CI] 6.39–60.83) and when PEP was not delivered the risks were higher in the pastoralist than the agro-pastoralist area (OR 6.12, 95% CI 2.60–14.58). Low socioeconomic class and distance to medical facilities lengthened delays before PEP delivery. Over 20% of rabies-exposed individuals did not seek medical treatment and were not documented in official records and <65% received PEP. Animal bite injury records were an accurate indicator of rabies exposure incidence.
Insufficient knowledge about rabies dangers and prevention, particularly prompt PEP, but also wound management, was the main cause of rabies deaths. Education, particularly in poor and marginalized communities, but also for medical and veterinary workers, would prevent future deaths.
Thousands of human deaths from rabies occur annually despite availability of effective vaccines for humans following exposure, and for disease control in domestic dog populations. We established a 5-year contact-tracing study in northwest Tanzania to investigate risk factors associated with rabies exposure and to determine why human deaths from canine rabies still occur. We found that children were at greater risk of being bitten and of developing rabies than adults and that incidence of bites by suspected rabid animals was higher in an area with larger domestic dog populations. A large proportion (>20%) of those bitten by rabid animals are not recorded in official records because they do not seek post-exposure prophylaxis (PEP), which is crucial for preventing the onset of rabies. Of those that seek medical attention, a significant proportion do not receive PEP because of the expense or because of hospital shortages; and victims who are poorer, and who live further from medical facilities, typically experience greater delays before obtaining PEP. Our work highlights the need to raise awareness about rabies dangers and prevention, particularly prompt PEP, but also wound management. We outline practical recommendations to prevent future deaths, stressing the importance of education, particularly in poor and marginalized communities, as well as for medical and veterinary workers.
Rabies is an acute viral infection which causes horrifying neurological symptoms that inevitably result in death. Although human rabies encephalitis remains untreatable
Recent estimates of human rabies mortality are based upon a probability decision-tree model
Data was collected from two rural districts in northwest Tanzania: Serengeti, which is inhabited by multi-ethnic, agro-pastoralist communities and high-density dog populations, and Ngorongoro, which is inhabited by low-density pastoralist communities and lower density dog populations. Contact tracing of potential rabies-exposures was initiated using data from hospitals and medical dispensaries on patients with animal-bite injuries, and case reports from livestock offices and community-based surveillance activities. Visits were made to investigate incidents that occurred between January 2002 and December 2006 involving potentially suspect rabid animals. Interviews were conducted to assess the case history and identify the source of exposure and other contacts if known. The same procedure was followed for all resulting exposures and preceding cases where identified, and UTM coordinates were recorded at each household and at the location of the exposure event (where possible). Interviews were conducted by veterinary or livestock field-officers, often with a community leader in attendance. This created an active local reporting network. Animal cases were diagnosed on epidemiological and clinical criteria adapting the ‘six-step’ method through retrospective interviews with witnesses
A structured open-ended questionnaire was administered to bite victims at 3 designated district hospitals (in Magu, Misungwi and Tarime, n = 166) to obtain information on intervals between exposure and reporting to hospital for PEP, and ways used to raise funds to pay for PEP. Information was collected on household socioeconomic status, using indicators sensitive to local determinants of wealth, previously identified through Rapid Rural Appraisal approaches
The study was approved by the Tanzania Commission for Science and Technology with ethical review from the National Institute for Medical Research (NIMR). In Tanzania, NIMR ethical guidelines stipulate that written consent is required for participants in clinical trials. However, as this was a retrospective study involving collection of interview data only, without clinical intervention or sampling, 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 only subsequently conducted following verbal consent from both the head of the household and the bite victim.
Bite-injury records were compiled for hospitals in Serengeti and Ngorongoro districts and neighboring districts of Tarime, Musoma and Bunda. Records were extracted for patients originating from Serengeti and Ngorongoro and correlations with rabies exposures and observations of rabid animals were examined by regression. Fisher's Exact Test was used to determine whether any factors were associated with delays in PEP delivery and to assess differences in the source of funds used to pay for PEP by different socioeconomic classes. Binomial confidence intervals were reported for proportions. Chi-square tests were used to examine differences in exposure incidence across age-classes, and to different parts of the body. The odds of developing rabies following exposure and associated risk factors were calculated by logistic regression. All statistical analyses were implemented with the statistical programming language R.
1080 people were traced and interviewed who had been bitten by animals between 2002 and 2006 in Serengeti (776) and Ngorongoro (304) districts. On the basis of descriptive case histories >97% of animals that caused bite injuries were classified as suspected rabid (648) or normal (406). The status of animals that bit the remaining 2.5 percent (26) of cases visited was unclear. Approximately 75% of samples from suspected rabid animals tested positive, indicating that recognition of rabies is accurate and that classification using the case history description is valid
Conservative estimates suggest around 63/100,000 people in Serengeti and 17/100,000 in Ngorongoro are bitten by suspected rabid animals annually. Including animals of undetermined status raises those figures to 100 and 30 exposures/100,000 respectively. The risk of being bitten by a suspected rabid animal varied through time (approaching 150/100,000 during the epidemic peak), but was consistently higher in Serengeti, the more populated district (
Bites/ 100,000 | Deaths/ 100,000 | |||||
Serengeti District | Ngorongoro District | Serengeti District | Ngorongoro District | |||
Year | lower | Upper | lower | upper | ||
2002 | 17.78 | 24.09 | 8.14 | 18.50 | 1.15 | 1.48 |
2003 | 111.80 | 135.84 | 43.48 | 54.18 | 1.12 | 4.28 |
2004 | 94.80 | 140.57 | 19.23 | 37.77 | 2.72 | 2.06 |
2005 | 49.92 | 90.28 | 7.94 | 29.11 | 1.06 | 1.32 |
2006 | 40.89 | 108.18 | 5.74 | 11.47 | 1.55 | 0.64 |
63.04 | 99.79 | 16.91 | 30.21 | 1.51 | 2.29 | |
0.02 | 0.12 |
Lower estimates are based on successfully traced exposures determined to be from suspected rabid animals and records that indicated the bite was caused by an animal suspected to be rabid. Upper estimates include bite injuries where the status of the biting animal was not recorded and the case has not been traced.
Species | Serengeti District (%) | Ngorongoro District (%) |
domestic dogs | 487 (85.6) | 84 (70.1) |
domestic cats | 26 (4.6) | 6 (5.0) |
Livestock | 7 (1.2) | 3 (2.5) |
Human | 2 (0.4) | 1 (0.8) |
Wildlife | 47 (8.3) | 26 (21.7) |
569 | 120 |
Numbers (and percentages) of exposures are shown.
Children were most at risk of exposure to rabies: 65% of exposures were children (<16 yrs, median 12, range 1–79); children from 5–15 years old had an elevated risk of exposure compared to the rest of the population (
The age distribution of suspected rabies bite victims (dark gray, n = 642) compared to the population as a whole in Serengeti and Ngorongoro districts (light gray, n = 307,099).
Age | Arm | Head | Leg | Trunk | Total |
0–10 yrs | 53 (2) | 23 (6) | 55 (2) | 24 (1) | 155 (11) |
10–20 yrs | 50 (4) | 8 (0) | 64 (3) | 13 (0) | 135 (7) |
20+ yrs | 41 (2) | 9 (0) | 64 (1) | 8 (0) | 122 (3) |
144 (8) | 40 (6) | 183 (6) | 45 (1) | 412 (21) |
Numbers in parentheses are rabies deaths. When the victim was bitten multiple times, the bite site closest to the head was listed.
Animal-bite injury records were correlated with suspected rabies exposures in both districts (
Records of patients from Serengeti and Ngorongoro districts.
Between 15 and 24% of suspected rabies exposures (169 people,
Exposed | Attended hospital | Received PEP | |
Traced cases | 699 | 530 (76%) | 456 (86%) |
Traced cases and cases of unknown status | 1140 | 971 (85%) | 685 (71%) |
The lower row also shows individuals bitten by animals of unknown status who have yet to be traced.
The cost of PEP and the regimen delivered varied depending upon the health facility and the date of presentation, varying from >100,000 Tsh (∼US$85) to free (for limited periods), although courses were typically 75,000 Tsh in Ngorongoro district (five doses) and 30,000 in Serengeti (3 doses), in comparison to monthly per capita expenditure and per household expenditure of 8,538 Tsh and 52,649 Tsh respectively in 2001
Most people who attended a medical facility did so shortly after exposure, but there was considerable variance in delays before receiving the first dose of PEP (
(A) Distribution of delays till first dose of PEP. (B) Delivery delays by distance from district hospital and (C) by socioeconomic status.
Four major means of raising funds for PEP were reported: i) family savings; ii) borrowing money; iii) selling household properties and iv) payment by the owner of the rabid animal. Socioeconomic status had a significant impact on the source from which households obtained funds (p<0.0001). Households with higher socioeconomic status were more likely to use savings, whereas households with low socioeconomic status either obtained loans from relatives, friends and neighbors or depended on the owner of dogs which inflicted the bites to pay (
Not all patients completed the PEP course, or adhered to the PEP schedule. Reasons given for not starting, completing or adhering to PEP regimes in the most commonly cited order were: i) unable to afford treatment; ii) no vaccine at the hospital; iii) the wound was small; iv) the dog owner would not pay; v) they were not aware the animal was rabid; vi) they were not aware of the danger of rabies; vii) medical staff did not advise PEP and viii) they thought they had received treatment but contact tracing revealed vaccination only against tetanus. Bite victims often quoted several reasons.
Twenty-eight deaths from suspected rabies were recorded during the five-year period in the two districts (
# | Age (yrs) | Sex | District | Source of exposure | Bite site and details | Circumstances | Incubation period | Duration of clinical signs | Description of clinical signs | Reason for not receiving PEP |
1 | 8 | m | N | Dog | Shoulder, severe | While herding | 3.5 m | 3.5 d | Strange vocalisations | |
2 | 5 | m | N | Dog | Back, severe | While herding | 4 d | Hypersalivation, strange vocalisations, ataxia | Referred to district hospital after symptoms began | |
3 | 7 | m | N | Dog | Face | While herding | 2 m | 12 d | Strange vocalisations, hypersalivation, fever, headache, abnormal sleep | |
4 | 14 | m | N | Dog | Arm, severe | While herding | 6 w | Received 4 doses | ||
5 | 6 | m | N | Dog | Face | While herding | 1 m | 12 d | Didn't realise dog was rabid | |
6 | 6 | m | N | Dog | Aggression and agitation, bit mother | |||||
7 | 13 | m | N | Hyena | Hand, arms, severe | Bathing in the river | 2 w | 3 d | Not advised at dispensary where wounds treated | |
8 | 4 | f | N | Dog | 1 m | Fever, confusion, convulsions | ||||
9 | 3 | m | N | Dog | The wound had healed | |||||
10 | 16 | m | N | Mongoose | Ankle, large septic wound | While herding | 2 m | Aggression, anxiety, confusion | Didn't realise danger | |
11 | 5 | f | N | Dog | Face | While herding | 3 w | 5 d | Strange vocalisations, hypersalivation | Advised to go to district hospital but it was too far |
12 | 50 | f | N | Cat | Hand and leg, severe | Bitten while in bed | 1 m | Strange vocalisations, hypersalivation, dysphagia | ||
13 | 6 | m | N | Honey badger | Head and hands | While herding with mother (who was also bitten) | 1 m | |||
14 | 7 | m | N | Dog | Fever | |||||
15 | 7 | m | S | Dog | While playing | 31 d | 5 d | Rashes, vomiting, fever, dysphagia, nervous, aggression, hypersalivation | Thought bitten by another healthy dog | |
16 | 8 | f | S | Dog | Hands and wrist | Returning from school | 33 d | 6 d | Aggression, hypersensitive, vomiting, aerophobia, bit father | Dog owner lied about dog |
17 | 45 | m | S | Dog | Finger, deep punctures | Bitten by his own puppy while at home | 29 d | 4 d | Fever, shouting, confusion, dysphagia | No money |
18 | 8 | f | S | Dog | Head, hands, very severe | Returning from school | 36 d | 8 d | Fever, nervous, dysphagia | PEP given the following day |
19 | 7 | m | S | Dog | Face, hand, back, very severe | Returning from school | 14 d | 3 d | Convulsing, vomiting, anxiety, dysphagia | PEP given the following day |
20 | 16 | m | S | Dog | Arm and fingers | Was bitten at home | 5 w | Attended hospital 10 days after bite | ||
21 | 45 | f | S | Dog | 2 w | |||||
22 | 15 | m | S | Honey badger | ||||||
23 | 12 | m | S | Dog | Hand and leg | 9 m | Aggression, bit mother | No PEP remaining so went to local healer | ||
24 | 11 | m | S | Dog | Leg, small | While playing outside house | 3 w | 4 d | Headache, rash, aching, ataxia, nervous, hypersensitive, aerophobia | Not advised treatment because minor wound |
25 | 5 | m | S | Dog | Foot and ankle, small | Outside house | 1 m | 2 d | Ataxia, biting | |
26 | 16 | m | S | Dog | Leg | 1 m | 3 d | Strange vocalisations, biting till gums bled | Dog owner refused to pay | |
27 | 16 | f | S | Cat | 2 m | Aggression, hit mother | Health-worker said cat was bewitched | |||
28 | 20 | m | S | Dog | Leg | While hunting at night | 3 m | 4 d | Did not realise dog was rabid | |
29 | 70 | f | S | Dog | Leg, severe | On way to village meeting | 69 d | 2 d | Paresthesia, strange vocalisations, agitation, pain | No money |
30 | 45 | f | S | Dog | Hand and face | Knocked down near house | 53 d | 1 d | Hypersalivation, hydrophobia | No money |
31 | 40 | f | S | Dog | Hand | Bitten at owners house | 55 d | Hypersalivation, headache, unable to swallow | Given possibly fake injections at dispensary |
Dog = domestic dog, Mongoose = white-tailed mongoose, m = month/s, w = week/s, d = day/s. Cases 29 to 31 occurred in 2007 and are not included in statistical analyses.
Three people who died from rabies received some PEP: two children in Serengeti district started PEP promptly (PEP was sought on the day of exposure, but delivered the following day because the medical facility was closed on weekends) and one teenager in Ngorongoro received the first dose of PEP several days after exposure and completed four doses before symptoms began. The vaccine in Ngorongoro district was tested and found to be viable. Vaccine was not available for testing in Serengeti but no other exposed patients died after receiving vaccine from the same batch. Moreover, the two children had severe injuries to the head, neck and spine, neither received immunoglobulins and the post-exposure regimen used was not WHO standard. One child developed symptoms shortly after receiving the second PEP dose and the second child died after completing the third dose. The remaining 25 cases did not receive any PEP, although at least 6 attended a medical facility promptly. Most rabies victims did not seek medical attention until after symptoms had begun, then in some instances the patient was taken to multiple medical centers in the hope of receiving a more positive prognosis. At least 5 cases (>17%) were initially diagnosed with cerebral malaria, but as symptoms progressed and when the history of a bite was discovered, the diagnosis was changed to rabies. Exposed individuals who developed rabies generally lived further from medical facilities than those who did not, although this was not statistically significant (p = 0.08). Risks of (and trauma from) human-to-human transmission are also not inconsequential; three rabies-infected individuals (>10%) bit a family member and a fourth hit her mother, apparently due to disease-induced changes including aggression. Additionally a twenty-year old woman died of tetanus following a suspected rabid dog bite. She developed symptoms of tetanus before completing her third dose of PEP. Because she was pregnant it was assumed that she must have been previously vaccinated against tetanus.
We investigated how risks of rabies exposure and onset of disease vary according to epidemiological and socioeconomic determinants and present evidence-based recommendations to reduce these risks in settings where canine rabies is endemic, addressing perspectives of both the health provider and patient
Numbers of suspected rabies exposures varied considerably through time and across districts. The temporal variation was presumably due to the tendency of the disease to fluctuate on a timescale of approximately five years
The higher risk of exposure in the more populated areas was likely due to the higher incidence of rabies and longer duration of outbreaks (and less frequent fade-out) in larger domestic dog populations (dog density: ∼11.4/km2 in Serengeti district versus 4.2/km2 in Ngorongoro district, which is close to the critical threshold for persistence ∼4.5/km2)
One of the greatest challenges for controlling canine rabies has been raising the priority of the disease. It is widely recognized that rabies is grossly under-reported even though it is notifiable and the lack of accurate figures has rendered rabies a low public health and veterinary priority. Previous attempts to quantify the burden of rabies have relied upon hospital records and have pointed out the need to verify their methods and conduct active case detection studies
Our results highlight key aspects of health services that could be targeted to improve the treatment of patients reporting with animal-bite injuries. For instance, many bite victims had to travel to hospitals in neighboring districts (sometimes several) to obtain PEP, prolonging delays before PEP delivery, increasing the risk of disease and incurring considerable costs on victims and their families. Improved surveillance combined with timely reporting and centralized responses for vaccine distribution could prevent PEP shortages and reduce the need to travel to alternative clinics. Animal-bite injury records are an accurate indicator of rabies exposures (exposure status is not regularly recorded) and therefore have potential to be used as a surveillance tool, but to be of most value, records ought to be collated over catchment areas spanning several districts. The number of cases where patients reporting to medical facilities were misadvised is also unacceptable indicating that medical personnel require greater training in recognizing cases of rabies exposure and in judicious administration of appropriate PEP.
The risk and burden of rabies falls disproportionately on the most vulnerable sectors of society: children and particularly those in marginalized pastoralist populations. The high proportion of childhood rabies deaths, a well-documented statistic
Zoonotic diseases are often neglected because the major burden falls within the health sector, yet the veterinary sector is usually responsible for their control. The two sectors typically operate independently and resources available to the medical sector are often much greater than those in veterinary departments. In reality rabies is a shared problem that can only be tackled by a multidisciplinary approach. Without laboratory confirmation and accurate diagnosis of animal rabies, public health authorities will not recognize rabies prevalence and without accurate information on human deaths and exposures from public health authorities the disease will not receive the attention it requires from the veterinary sector. One example that is a pervasive problem, evident in this and other studies
In accordance with the Regional East African Community Health (REACH) initiative's mission to access, synthesize, package and communicate evidence required for policy and practice to improve population health and health equity (
Awareness needs to be raised about the importance of immediately washing animal-bite wounds and reporting rapidly to medical facilities for PEP (irrespective of the size and severity of injury).
Supply and distribution systems for PEP should be reviewed because shortages are frequent, regional disparities exist in prices and regimen, and treatment cannot always be accessed during evenings and weekends.
Mechanisms should be sought to reduce the price of PEP and enable early initiation of treatment for patients who may be unable to quickly access sufficient funds to pay for PEP (e.g. use of economical intradermal PEP regimens
Improved training is needed for medical personnel to ensure awareness about the serious nature of rabies exposures and enable judicious decisions about PEP administration. Prophylaxis should be initiated immediately unless the patient is reporting more than ten days after exposure and is completely certain the biting animal is alive and healthy. Similarly PEP can be discontinued if the animal's good health can be established at subsequent hospital visits.
Collaborative (veterinary and medical) programs should be established to control and eliminate rabies from domestic dog populations and improve surveillance and diagnosis in both animal and human populations.
Translation of the Abstract into Swahili by M. Kaare.
(0.01 MB PDF)
We thank the Serengeti Viral Transmission dynamics team, the livestock field-officers of the Ministry of Water and Livestock Development and staff of district hospitals and dispensaries in Mara and Arusha Regions and local community members who provided invaluable assistance with data collection. Intervet supported the project through provision of dog vaccine, and Frankfurt Zoological Society, Sokoine University of Agriculture, and the Mwanza and Arusha Veterinary Investigation Centers all provided valuable logistical and technical support. We are grateful to Tanzanian Government ministries, TANAPA, TAWIRI, NCA Authority, Tanzania Commission for Science and Technology, and National Institute for Medical Research for permissions and D. Bennett for useful discussions.
Dr Magai Kaare played a critical role in the research leading to this publication and made an enormous contribution to rabies research and control in Tanzania. His loss is a tragedy and he will be greatly missed.