Developing and evaluating an intervention to improve care and reduce costs of rabies postexposure therapy: an observational quality improvement initiative in selected vaccination units in Sri Lanka.

BACKGROUND: Exposure to the rabies virus is fatal unless a patient is treated with a timely, accurate and complete administration of postexposure prophylaxis (PEP). The level of adherence to PEP guidelines by health service providers is therefore critical in providing high-quality care as well as preventing unnecessary costs. METHODS: We developed a simple user-friendly decision aid based on Sri Lankan national guidelines for the administration of PEP and trialed it over a 5-month period in three study settings. Pre and post levels of adherence to the national guidelines by service providers was measured in each setting. Changes to per patient cost for rabies medications and hospital admissions were also collected. RESULTS: A significant improvement in adherence to the guidelines was observed in two settings with a nonsignificant improvement observed in the third setting. We estimated a total cost saving of LKR 158 476 across the three sites, comprising LKR 14 418 in admissions cost savings and LKR 144 058 in medication savings. CONCLUSION: We conclude that the development of a decision aid for the administration of PEP is likely to be an effective and cost-saving intervention in the Sri Lankan setting. Further research is required to inform the generalizability of our findings.

Twelve years of rabies surveillance in Sri Lanka, 1999-2010.

BACKGROUND: Rabies is endemic in Sri Lanka, but little is known about the temporal and spatial trends of rabies in this country. Knowing these trends may provide insight into past control efforts and serve as the basis for future control measures. In this study, we analyzed distribution of rabies in humans and animals over a period of 12 years in Sri Lanka. METHODS: Accumulated data from 1999 through 2010 compiled by the Department of Rabies Diagnosis and Research, Medical Research Institute (MRI), Colombo, were used in this study. RESULTS: The yearly mean percentage of rabies-positive sample was 62.4% (47.6-75.9%). Three-fourths of the rabies-positive samples were from the Colombo, Gampaha, and Kalutara districts in Western province, followed by Galle in Southern province. A high percentage of the rabies samples were from dogs (85.2%), followed by cats (7.9%), humans (3.8%), wild animals (2.0%), and livestock (1.1%). Among wild animals, mongooses were the main victims followed by civets. The number of suspect human rabies cases decreased gradually in Sri Lanka, although the number of human samples submitted for laboratory confirmation increased. CONCLUSIONS: The number of rabid dogs has remained relatively unchanged, but the number of suspect human rabies is decreasing gradually in Sri Lanka. These findings indicate successful use of postexposure prophylaxis (PEP) by animal bite victims and increased rabies awareness. PEP is free of charge and is supplied through government hospitals by the Ministry of Health, Sri Lanka. Our survey shows that most positive samples were received from Western and Southern provinces, possibly because of the ease of transporting samples to the laboratory. Submissions of wild animal and livestock samples should be increased by creating more awareness among the public. Better rabies surveillance will require introduction of molecular methods for detection and the establishment of more regional rabies diagnostic laboratories.

Molecular epidemiology of human rabies viruses in Sri Lanka.

Rabies is a lethal zoonotic disease caused by the rabies virus, which is transmitted by rabid animals to humans. Rabies is prevalent in all continents, with over 60% of human deaths occurring in Asia. Sri Lanka is a rabies-endemic country. This study shows that rabies afflicted more older individuals than children in Sri Lanka between 2008 and 2010. This novel finding indicates that older people in Sri Lanka should be more aware of the risk of rabies. Phylogenetic analyses of the rabies N and G genes showed that the Sri Lankan rabies viruses are distinct and probably originated from a single clone. The G-L noncoding region is highly diverse, and is suitable for the analysis of virus evolution within a country. A phylogenetic analysis of this region showed high diversity in the currently circulating Sri Lankan rabies viruses, which can be divided into seven clades. Some clades are unique to a specific geographic region, whereas others occur at multiple locations. This indicates that the movement of dogs, the main rabies-transmitting animal in Sri Lanka, is restricted in some areas but less limited in others. These data may help to formulate a more efficient rabies control program in Sri Lanka.

Evaluation of a monoclonal antibody-based rapid immunochromatographic test for direct detection of rabies virus in the brain of humans and animals.

Rabies diagnosis uses a direct fluorescent antibody test (FAT) that is difficult, costly, and time-consuming, and requires trained personnel. We developed a rapid immunochromatographic test (RICT) for the diagnosis of rabies. The efficacy of the RICT was compared with that of the FAT. Brain samples were collected from humans, dogs, cats, and other animals in Sri Lanka (n = 248), Bhutan (n = 27), and Thailand (n = 228). The sensitivity (0.74-0.95), specificity (0.98-1.0), positive predictive value (0.98-1.0), negative predictive value (0.75-0.97), accuracy (0.91-0.98), and kappa measure of agreement (0.79-0.93) were all satisfactory for animal samples and samples preserved in 50% glycerol saline solution. Because the RICT showed high sensitivity but low specificity with human brain samples, it is unsuitable for confirming rabies in humans. No amino acid substitutions were found in the antibody attachment sites of the nucleoprotein gene with FAT-positive, RICT-negative samples. The RICT is reliable, user friendly, rapid, robust, and can be used in laboratories with a modest infrastructure.

Evaluation of an improved rapid neutralizing antibody detection test (RAPINA) for qualitative and semiquantitative detection of rabies neutralizing antibody in humans and dogs.

Using the principle of immunochromatography, we previously developed a method called RAPINA (Rapid Neutralizing Antibody detection test) that can measure the level of rabies virus -neutralizing antibody (VNA) in serum samples [Shiota S, Mannen K, Matsumoto T, Yamada K, Yasui T, Takayama K, et al. Development and evaluation of a rapid neutralizing antibody test for rabies. J Virol Methods 2009;161:58-62]. RAPINA is faster, simpler, and easier to perform compared with a virus-neutralizing test or enzyme-linked immunosorbent assay (ELISA). The improved version of RAPINA has greater positive and negative predictive values corresponding to a VNA level of 0.5 IU/mL, as recommended by the World Health Organization and the World Organization for Animal Health. To verify the efficacy of this improved method, serum samples were collected from humans and dogs before and after immunization against rabies and were tested in Japan, Sri Lanka, and Thailand. The results were compared between RAPINA and the true VNA levels measured by the Rapid Fluorescent Focus Inhibition Test (RFFIT). The improved RAPINA accurately predicted seropositivity for 182 of 183 seropositive human samples as assessed by RFFIT (99.5%) and for 138 of 140 RFFIT-negative human samples (98.6%). In dog serum samples, the positive and negative predictive values were 99.7% (345/355) and 95.6% (174/182), respectively. RAPINA was also used to estimate VNA levels in a semiquantitative manner by using serial dilution of serum samples. Our results show that RAPINA is an easy and rapid method for measuring VNA levels before and after immunization with the rabies vaccine and does not need a high skill level or sophisticated equipment. RAPINA can be used to monitor the success of preexposure prophylaxis in at-risk persons, vaccine coverage, and animal control. It can also be used in laboratories with modest facilities and where a large number of samples are screened.

Novel sylvatic rabies virus variant in endangered golden palm civet, Sri Lanka.

Information is scarce about sylvatic rabies virus in Asia and about rabies in palm civets. We report a novel sylvatic rabies virus variant detected in a golden palm civet in Sri Lanka. Evolutionary analysis suggests the virus diverged from canine rabies viruses in Sri Lanka in ≈1933 (range 1886-1963).

Whole-genome analysis of a human rabies virus from Sri Lanka.

The complete genome sequence of a human rabies virus, strain H-08-1320, from Sri Lanka was determined and compared with other rabies viruses. The size of the genome was 11,926 nt, and it was composed of a 58-nucleotide 3' leader, five protein genes--N (1353 nt), P (894 nt), M (609 nt), G (1575 nt), and L (6387 nt)--and a 70-nt 5' trailer. The intergenic region G-L contained 515 nt. The sizes of the nucleoprotein, phosphoprotein, matrix-protein, glycoprotein and large-protein was 450, 296, 202, 524 and 2,128 residues, respectively. The phosphoprotein and large protein were one amino acid shorter and longer, respectively, than those of most rabies viruses. The glycoprotein of H-08-1320 had a unique amino acid substitution at antigenic site I. Whole-genome phylogenetic analysis showed that strain H-08-1320 formed an independent lineage and did not cluster with rabies viruses from other countries.

Rabies awareness in eight Asian countries.

Rabies is a deadly zoonotic disease most often transmitted to humans through a dog bite. Human mortality from endemic canine rabies is estimated by WHO to be around 55,000 deaths annually, with over 31,000 deaths in Asia alone, mostly children. Most of these deaths could be prevented through post-exposure prophylaxis (PEP), including immediate wound washing, rabies immunoglobulin administration and vaccination. Unfortunately, at-risk populations are not well-informed of the risk of rabies and what to do in the event of an animal bite. In order to identify the main gaps in rabies information and better define the most urgent information actions to be undertaken, the Asian Rabies Expert Bureau (AREB) conducted a multicentre, multi-country survey of patients seeking rabies post-exposure prophylaxis in rabies prevention centres from 1 July 2007 to 31 January 2008, in Bangladesh, China, India, Indonesia, Pakistan, the Philippines, Sri Lanka, and Thailand. Questionnaires were completed for 4377 subjects in the eight countries. Data was collected regarding the patient, former rabies exposures, the present wound, rabies exposure management, and rabies awareness. Two major issues were identified where active information of the population could make a difference: the necessity to apply appropriate wound care and to consult the nearest rabies prevention centre as soon as possible.

WHO informal consultation on the scientific basis of specifications for production and control of inactivated Japanese encephalitis vaccines for human use, Geneva, Switzerland, 1-2 June 2006.

The World Health Organization (WHO) publishes technical guidance on the quality, safety and efficacy of vaccines intended to assist national regulatory authorities and manufacturers. As part of its programme, WHO convened an informal consultation to initiate revision of the WHO recommendations on the production and control of inactivated Japanese encephalitis (JE) vaccines for human use, at its headquarters in June 2006. The attendees included experts from national regulatory authorities, national control laboratories and manufacturers from around the world as per WHO policy to include all relevant stakeholders in the standards development process. Issues pertaining to recent development with inactivated JE vaccines were presented and discussed. Participants agreed upon the scientific basis of revised specifications and the inclusion of new sections on nonclinical and clinical evaluation of inactivated JE vaccines. It was agreed that the revision would cover both existing vaccines derived from mouse brain or primary cell cultures and vaccines under development in a continuous cell line (Vero).

A global perspective on vaccine safety and public health: the Global Advisory Committee on Vaccine Safety.

Established in 1999, the Global Advisory Committee on Vaccine Safety advises the World Health Organization (WHO) on vaccine-related safety issues and enables WHO to respond promptly, efficiently, and with scientific rigor to issues of vaccine safety with potential global importance. The committee also assesses the implications of vaccine safety for practice worldwide and for WHO policies. We describe the principles on which the committee was established, its modus operandi, and the scope of the work undertaken, both present and future. We highlight its recent recommendations on major issues, including the purported link between the measles-mumps-rubella vaccine and autism and the safety of the mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of thiomersal-containing vaccines.