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The science of rabies in tropical regions: From epidemiological pandemonium to prevention The science of rabies in tropical regions: From epidemiological pandemonium to prevention
Gundamaraju, Rohit; Vemuri, Ravi Chandra; Sau Kuen, Lam; Manikam, Rishya; Singla, Rajeev K.; Sekaran, Shamala Devi; Chakrapani, Ramesh
2015-07-03 00:00:00
Frontiers in Life Science, 2015 Vol. 8, No. 3, 210–214, http://dx.doi.org/10.1080/21553769.2015.1041186 a∗ a b c d Rohit Gundamaraju , Ravi Chandra Vemuri , Lam Sau Kuen , Rishya Manikam , Rajeev K. Singla , Shamala Devi a e Sekaran and Ramesh Chakrapani a b Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; Department of Trauma and Emergency, University Malaya Medical Center, Kuala Lumpur 59100, Malaysia; Department of Biotechnology, Netaji Subhas Institute of Technology, Azad Hind Fauz Marg, Sector-3, Dwarka, New Delhi 110078, India; Department of Clinical Research, Sicra Institute of Clinical Research, Hyderabad, India (Received 12 October 2014; accepted 12 April 2015 ) Rabies is a devastating viral disease affecting the central nervous system. The fatality rate is very high compared to other viral diseases. Inadequate vaccination, lack of awareness, cost of medications and ineffective post-prophylactic surveillance are some of the major reasons for the high prevalence of rabies in tropical regions, leading to more than 40,000 cases annually presenting a major threat to public health. The present report aims to provide an overview of the lethal effects of rabies in major regions of the tropics, such as China and its neighboring countries, India, Bangkok, Thailand, all major regions of Africa, such as Tanzania and Ethiopia, and tropical regions of South America. The review is based on rich literature sources including epidemiological and endemic surveys, sample analysis, and health and hygiene reports from various parts of the world. The epidemiology is elucidated in the present article. The review also highlights the incidence of cases and aspects of prophylaxis. A bird’s-eye view of rabies and its epidemic impact will encourage researchers to act further on the disease, which will lead to better awareness and treatment options. Keywords: rabies; epidemiology; public health; tropical region; prophylaxis Introduction & Charlton 1988). Rabies can be transmitted not only by Rabies, from the Latin word for madness, is a viral disease dogs, but also by other animals such as weasels, bears, rac- that causes deadly maladies such as encephalitis in ani- coons, skunks and other wild carnivores. Small rodents, mals (Drew 2009). The disease is generally transmitted to such as squirrels, hamsters, guinea pigs, gerbils, chip- humans from other species (such as dogs), commonly by a munks, rats and mice, and lagomorphs, such as rabbits and bite from an infected animal. Rabies is fatal to humans if hares, are also transmitters of the virus. Many tourists catch prophylaxis is not administered before the onset of severe rabies (Taylor 1993; McRuer & Jones 2009); every year, symptoms. The rabies virus infects the central nervous sys- people visiting Thailand and other oriental countries are tem (CNS), causing disruptions in the brain and finally affected by the virus. leading to death (Drew 2009). The rabies virus turns deadly when it enters the human The major symptoms of rabies are headache, fever, body. When the virus reaches the brain, it rapidly causes severe acute pain, excitement, hydrophobia, lethargy in encephalitis, the prodromal phase, with the onset of symp- the later stages, coma and finally death, which is gen- toms. Once the symptoms appear in the patient, treat- erally due to respiratory failure (Cotran et al. 2005). ment is almost impossible. The probability of mortality Approximately 60,000 deaths are recorded annually world- at this stage is over 99%. Rabies may also inflame the wide (WHO 2011). Ninety-five percent of human deaths spinal cord, producing transverse myelitis (Larry et al. due to rabies occur in Asia and Africa alone (WHO: 2005). http://www.who.int/rabies/en). Dogs are responsible for This lethal transmission has been a public health con- 97% of human rabies cases (Voice of America 2009). cern for centuries. Many governing bodies, such as the Rabies elimination has been carried out in several coun- Centers for Disease Control (CDC), have been working to tries, including Australia, Japan and Singapore. improve public health. Deadly transmission What the virus does Apart from the dog (Canis lupus) (Figure 1), the rabies The virus enters the salivary glands of dogs before their virus also acclimatizes in cold-blooded animals (Campbell death from rabies. Other possible routes of transmission *Corresponding author. Email: rohit.gundamaraju@gmail.com © 2015 Taylor & Francis Frontiers in Life Science 211 also important potential transmitters of rabies (Jiang et al. 2010). Tropical Asian countries are notable for the spread of the virus not only among residents, but also in tourists, who are most susceptible to the virus. A novel study on backpackers (Watcharapong et al. 2010) highlighted the percentage risk of transmission of rabies to the travelers. The study focused on the attitude and awareness of the travelers, and these factors were found to play a role in the spread of the disease (Watcharapong et al. 2010). Although international guidelines recommend pre-exposure to the rabies vaccine, only 18.1% of people in the study had been vaccinated. Nearly 70% of the people never obtained rabies Figure 1. A rabies-infected dog. Source: http://en.wikipedia. immunization, and the major reason for the lack of immu- org/wiki/Rabies#/media/File:Dog_with_rabies.jpg. Content Pro- viders: CDC/Barbara Andrews [public domain]. nization was the cost of the vaccine. Rabies vaccination is necessary if travelers are either moving to rabies-prone areas or staying for a period of more than 10 days. In the include contamination of mucous membranes, aerosol study by Watcharapong et al. (2010), half of the exposures transmission and corneal transplantation. The incubation took place within the first 10 days. Such studies confirm period may range from 10 days to many years. However, the need for health education and awareness of this deadly it depends mostly on the distance of the wound from the disease (Krause et al. 1999). Pre-exposure would be a bet- CNS. The virus moves in the nerves to reach the brain ter strategy than seeking medical assistance after a bite, as and other multiple locations. The final location is the effer- many areas in tropical Asian countries lack medical and ent nerves, from which it can move to the salivary glands. immunization facilities. In the Watcharapong et al. (2010) Rabies virus infection forms cytoplasmic inclusion bodies study, only four of the backpacking travelers who were bit- similar to Negri bodies, which are considered to be the sites ten by dogs managed to obtain medical aid. Studies have of viral transmission and replication (Larry et al. 2005). confirmed that only 64% of the public hospitals in Thailand have stocks of rabies immunoglobulin (Kositprapa et al. 1998). Other South Asian countries also have limited med- Epidemiological devastation and concerns ical facilities and a lack of rabies immunization (Wilde Almost all recorded deaths due to the rabies virus occur in et al. 2005; Ly et al. 2009). Therefore, travelers should developing countries, and 80% of fatalities occur in Asia have proper awareness of rabies and be pre-immunized for (Knobel et al. 2005; Zhenyang et al. 2013). India has the their own benefit. highest number of rabies cases in humans, followed by Figure 2 shows the geographical distribution of rabies. China, which has seen more than 117,500 deaths since The figure highlights areas in eastern Africa, e.g. Ethiopia, 1950 (Tang et al. 2005). Owing to reasons like poor dog China and neighboring countries, and other countries control, in Asia 85–90% of cases are due to transmission including Thailand, using data from previous epidemic and of the virus through dog bites (Tao et al. 2009; Nadin endemic studies. et al. 2011). Rabies virus collected from China shares genetic characteristics with its ancestors (Yamagata et al. 2007; Shao et al. 2011; Zhenyang et al. 2013). Zhenyang et al. (2013) affirmed the phylogenetic variations and rela- tionships between different strains collected in China and neighboring countries. Multiple sampling and broader iso- lation techniques were incorporated in this study to over- come problems of limited sampling (Zhenyang et al. 2013). Some clustered clades with isolates from countries in the Indochina peninsula and mainland Southeast Asia were observed, suggesting that this may be a convergent region for rabies virus panmixis owing to frequent animal trade between neighboring countries. Migration of people from villages to towns, and from towns to cities, with their domestic dogs could be another reason for the spread of the virus. Increased domestication of dogs and a remarkable increase in dog meat markets are contributing to the esca- Figure 2. Major rabies threats in the Asia Pacific and African regions. lation of rabies prevalence (Zhenyang et al. 2013). Bats are 212 R. Gundamaraju et al. sequence-based amplification, direct rapid immunohisto- chemical tests and isolation of the virus from the cere- brospinal fluid or saliva. Antibodies can be detected in the serum and cerebrospinal fluid. Pathological specimens often demonstrate round or oval eosinophilic inclusion bodies in the cytoplasm of neuronal cells (Angela et al. 2011). Prevention by pre-exposure immunization This process includes treating people with three intramus- cular injections of human diploid cell vaccine (1 ml on days 0 and 7, and 21 or 28), especially those who are at a high risk of exposure. Backpackers who explore countries Figure 3. Overall numbers of different modes of transmission of in Africa, Asia, and other high-risk areas should receive rabies. an intradermal dose, over the deltoid, on days 0, 7 and 21 (Maxine et al. 2013). After Asia, Africais in second place in the spread of rabies in humans and domestic animals (Jemberu et al. Post-exposure immunization 2013). In Africa, Ethiopia has one of the highest levels of The patient is generally treated on the basis of the extent of endemic rabies. With regard to the incidence of deaths due to rabies, Ethiopia is one of the worst affected countries in the bite, intensity, location of the wound, animal, history the world, having 10,000 deaths annually (Fekadu 1997). of previous immunization and epidemiology. Immediate Africa suffers huge losses of livestock due to rabies (Kno- consultation with local health departments is highly rec- bel et al. 2005). Jemberu et al. (2013) conducted a thorough ommended. The optimal form of passive immunization is a study which included a survey of the area, a questionnaire human rabies immunoglobulin (HRIG; 20 IU/kg), admin- on practices and people’s knowledge and awareness, and istered once. The full dose is administered around the the incidence of rabies, both epidemically and endemically. wound (Maxine et al. 2013). Equine rabies antiserum (40 Although the total number of cases was highest in dogs, IU/kg) is used as an alternative. As much as possible of humans were supposed to be at higher risk than other ani- the rabies immunoglobulin is injected at the site of the mals (Figure 3). According to the rabies exposure charts wound and the remainder at a site distant from the vaccine in various districts, humans were exposed to the greatest administration. extent. After Ethiopia, Kenya and Tanzania have the next At present, purified vaccines are grown on Vero cells, highest incidence of rabies (Kitalaa et al. 2000; Cleaveland and a sixth generation Vero cell vaccine is under devel- opment. This method produces more allergy-resistant vac- et al. 2002). Among all the cases recorded, and with regard cines compared to the previous chicken embryo cell-grown to their severity, most of the cases were from rural areas vaccines. HRIG is unnecessary in previously vaccinated as the people and livestock had a high risk of exposure. patients. The post-exposure vaccine includes 1 ml in the Dogs were found to be the major reservoir and source of deltoid, administered twice (on days 0 and 3). Post- infection. exposure prophylaxis (PEP) is considered safe and does not In Africa, Ethiopia had some of the rarest encounters, even cause fetal complications (CDC 2011; Maxine et al. which most people would never have thought possible, 2013). including human-to-human rabies transmission (Fekadu et al. 1996). A case of rabies was recorded in two indi- viduals of the same family and the disease was likely Need for elimination and ways of prevention to have been spread by human-to-human transmission. As the rabies virus is spread mainly by domestic dogs, However, the high incidence of rabies in areas like the elimination of the virus is the best option (Lembo et al. Serengeti district (Tanzania, Africa) was due to domes- 2010). The virus can be eliminated by mass vaccination tic dogs (Hampson et al. 2008), whereas in areas like the (Coleman & Dye 1996). Ngorongoro district of Tanzania the high prevalence of Figure 4 illustrates the spread and reported cases of rabies was more likely to be due to the high proportion of rabies in China. It is evident that the numbers of cases have wildlife (Cleaveland & Dye 1995). been significantly and consistently increasing, thus provok- ing the need for the elimination of the virus to stop the Laboratory confirmation, prophylaxis and treatment spread of this disease. Definitive diagnostic assays include quantitative reverse Shanghai was one region of China in which the transcriptase–polymerase chain reaction, nucleic acid post-exposure vaccination coverage was about 99% Frontiers in Life Science 213 Figure 4. Reported cases of rabies in China during 2007–2012 (extracted from Wenwu et al. 2013). (Wenwu et al. 2013). However, lack of awareness of the supplies, have been implemented (PAHO 2011). It has vaccine and lack of medical facilities in areas like Guizhou been crucial to understand the rabies life cycle and design and Guangdong is evident, as nearly 1000–2020 cases of an appropriate treatment path. rabies were recorded. A Chinese survey on injuries in chil- Other rabies elimination programs have been imple- dren, conducted among 319,543 people (including 98,335 mented in India, such as the street dog sterilization pro- children aged < 18 years) in Jiangxi province in 2007, gram. Information on street dog breeding was analyzed by estimated that 89 children may have died of animal (mainly experts in the Jaipur region in India. Animal bites and their dog) bites, whereas China CDC reported 21 rabies cases correlation with the season were also estimated. Under this (i.e. four-fold underreporting) in the same year and the program, dog bites have decreased significantly since 2003 same age group (Wenwu et al. 2013). and the roaming dog population has been reduced (Reece Previous elimination principles included controlling et al. 2013). rabies in dogs, providing access to adequate PEP in humans Many tropical countries need to implement 100% pre- to ensure effective disease control, and animal reser- prophylaxis and other similar procedures to reduce the voir surveillance throughout the course of the campaign numbers of rabies cases. Successful strategies have to (Wenwu et al. 2013). be put in place, including issuing biological supplies to The need for elimination in South American coun- rural areas, running awareness camps and conducting mass tries was also high. A high proportion of people who vaccination programs. were affected in South American cities were low-income individuals (Vigilato et al. 2013). As a result, a num- ber of canine vaccination programs have been arranged in Conclusion South American cities. Nearly 81% of animals were vac- Today, many countries are facing rabies as an endemic cinated from 2001 to 2003. Latin American and tropical and epidemic challenge. Establishing intensive surveil- countries such as Brazil, Venezuela and Argentina have lance, awareness protocols and communication with local participated in these programs. More than 2,500,000 doses communities can only aid in eradicating the disease. of human vaccine have been used annually in pre- and post-prophylaxis (PAHO 2011; Vigilato et al. 2013). Key procedures, such as technical cooperation, quality assur- Funding ance of biological products, providing a motivated staff, SD and RG are grateful to the University of Malaya for research control of the canine population, establishing early pro- grant UMRG356/11HTM, providing the support to write this review article. 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