Background: Costs of rabies post-exposure prophylaxis (PEP) often remain high in regions where rabies has been controlled in dogs, presenting a challenge for sustaining rabies elimination programmes. We investigated the potential for bite patient risk assessments to improve PEP provision and surveillance in settings approaching elimination of dog-mediated rabies. Methods: We conducted a longitudinal study of patients presenting to animal bite treatment centres (ABTCs) on the island province of Bohol in the Philippines to investigate the health status of biting dogs and to quantify current expenditure on PEP. Results: Incidence of bite patients presenting to ABTCs was high (>300/100,000 persons/year) and increasing, resulting in substantial health provider costs. Over $142,000 was spent on PEP in 2013 for a population of 1.3 million. From follow up of 3820 bite patients we found that >92% were bitten by healthy dogs (alive 14 days after the bite) and just 1.4% were bitten by probable or confirmed rabid dogs. The status of dogs that bit 6% of patients could not be determined. During the course of investigations of bites by suspect dogs, we were able to obtain samples for case confirmation, identify exposed persons who had not sought PEP as well as in-contact dogs at risk of developing rabies. We calculate that expenditure on PEP could at least be halved through more judicious approaches to provision of PEP, based on the histories of biting animals determined through risk assessments with bite patients. Conclusions: We conclude that a One Health approach to surveillance based on Integrated Bite Case Management could improve the sustainability and effectiveness of rabies elimination programmes while also improving patient care by identifying those genuinely in need of lifesaving PEP. (C) 2019 The Authors. Published by Elsevier Ltd.

Rabies is endemic in the Philippines. In 2010, with support from the Bill and Melinda Gates Foundation, a canine rabies elimination project was initiated in the Philippine Archipelago of Visayan. We conducted an analysis of dog vaccination and human PEP costs for dog bite patients in a highly urbanized area and a low-income rural municipality in Cebu Province, Philippines, from 2010 to 2012. Our findings indicated that eliminating rabies in dogs through mass vaccination is more cost-effective than treating rabies exposures in humans. The average costs (in USD) per human life saved through PEP were $1620.28 in Cebu City and $1498 in Carmen. Costs per dog vaccinated ranged from $1.18 to $5.79 in Cebu City and $2.15 to $3.38 in Carmen. Mass dog vaccination campaigns conducted in each village were more cost-effective than fixed-site campaigns. The costs of dog vaccination can be reduced further through bulk vaccine purchase by the national government or large donor agency, for example the BMGF. As communities achieve canine rabies elimination, more judicious use of PEP will result in significant public savings. The study affirms the willingness of local governments to invest and reassure donors of their cooperation and resource contribution to sustain disease elimination efforts.

Knowledge, attitudes, and practices (KAP) regarding rabies in Bohol, Philippines were assessed following introduction of the Bohol Rabies Prevention and Elimination Programme. A cross-sectional questionnaire was administered to 460 households chosen utilizing the WHO's Expanded Programme on Immunization coverage cluster survey technique with population proportionate to size. Scores for KAP were evaluated using linear regression. The majority of households had heard of rabies (94%); however, specific knowledge of rabies was limited. Only 18% knew to report a suspected rabid dog to the authorities. In multivariate analyses, having known someone with rabies had the greatest effect on knowledge scores. Employment (professional or non-professional) had the greatest effect on attitudes scores, and only the knowledge score was significantly associated with higher practices scores. Several factors, notably, personal experience with rabies, affect KAP in Bohol. The programme should continue to focus on education and include personal accounts to underscore why rabies prevention and control is so important.

SummaryThe Philippines has a long history of rabies control efforts in their dog populations; however, long‐term success of such programmes and the goal of rabies elimination have not yet been realized. The Bohol Rabies Prevention and Elimination Program was developed as an innovative approach to canine rabies control in 2007. The objective of this study was to assess canine rabies vaccination coverage in the owned‐dog population in Bohol and to describe factors associated with rabies vaccination 2 years after implementation of the programme. We utilized a cross‐sectional cluster survey based on the World Health Organization’s Expanded Programme on Immunization coverage survey technique. We sampled 460 households and collected data on 539 dogs residing within these households. Seventy‐seven per cent of surveyed households reported owning at least one dog. The human‐to‐dog ratio was approximately 4 : 1, and the mean number of dogs owned per household was 1.6. Based on this ratio, we calculated an owned‐dog population of almost 300 000. Overall, 71% of dogs were reported as having been vaccinated for rabies at some time in their lives; however, only 64% of dogs were reported as having been recently vaccinated. Dogs in our study were young (median age = 24 months). The odds of vaccination increased with increasing age. Dogs aged 12–23 months had 4.6 times the odds of vaccination compared to dogs aged 3–11 months (95% CI 1.8–12.0; P = 0.002). Confinement of the dog both day and night was also associated with increased odds of vaccination (OR = 2.1; 95% CI 0.9–4.9; P = 0.07), and this result approached statistical significance. While the programme is on track to meet its goal of 80% vaccination coverage, educational efforts should focus on the need to confine dogs and vaccinate young dogs.

Rabies is probably the oldest---recognized and most---feared disease that affects humans. It is obvious from ancient texts and artwork dating back to the 23rd century BC that humans thousands of years ago clearly recognized the transmission cycle and signs of rabies. The disease is transmitted in the saliva of infected animals, most often introduced into the body by a bite wound. Historically, most human rabies cases occurred as a result of the bite of rabid dogs or wild carnivores. In modern times in developed countries, rabies has been well controlled by mandatory vaccination of pet dogs and cats. Since vaccination of pet animals became routine, human rabies cases have fallen dramatically and are now considered rare in the U. S. Cases of human rabies occurring in the U.S. today involve contact with non---pet reservoir animals, as well as cryptic cases which are presumed to have originated by some form of contact with wild reservoir animals. Clearly, a small but significant risk of contracting rabies persists for individuals who come into contact with reservoir animals.

We developed an immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), using partial recombinant nucleoproteins (rNP) of Reston Ebola virus (EBO-R) and Zaire Ebola virus (EBO-Z). We examined the reaction of 10 sera from cynomolgus macaques naturally infected with EBO-R to each of the partial rNP in the IgG ELISA. All the sera reacted to the C-terminal halves of the rNP of both EBO-R and EBO-Z. Most of the sera reacted to the RΔC (amino acid (aa) 360–739), and RΔ6 (aa 451–551) and/or RΔ8 (aa 631–739) at a higher dilution than to the corresponding truncated rNPs of EBO-Z. The results indicate that this IgG ELISA is useful for detecting EBO-R specific antibody, and may have a potential to discriminate EBO-R infection from other subtypes.

Active surveillance for lyssaviruses was conducted among populations of bats in the Philippines.The presence of past or current Lyssavirus infection was determined by use of direct fluorescent antibody assays on bat brains and virus neutralization assays on bat sera.Although no bats were found to have active infection with a Lyssavirus, 22 had evidence of neutralizing antibody against the Australian bat lyssavirus (ABLV).Seropositivity was statistically associated with one species of bat, Miniopterus schreibersi.Results from the virus neutralization assays are consistent with the presence in the Philippines of a naturally occurring Lyssavirus related to ABLV.

With the increase in international traffic, the risk of introducing rare but severe infectious diseases like Ebola hemorrhagic fever is increasing all over the world. However, the system for the diagnosis of Ebola virus infection is available in a limited number of countries. In the present study, we developed an Ebola virus antigen-detection enzyme-linked immunosorbent assay (ELISA) system using a novel monoclonal antibody (MAb) to the nucleoprotein (NP). This antibody recognized an epitope defined by a 26-amino-acid stretch near the C terminus of NP. In a sandwich ELISA system with the MAb, as little as 30 ng of purified recombinant NP (rNP) was detected. Although this MAb was prepared by immunization with rNP of subtype Zaire, it also reacted to the corresponding region of NP derived from the Reston and Sudan subtypes. These results suggest that our ELISA system should work with three of four Ebola subtypes. Furthermore, our ELISA system detected the NP in subtype Reston-infected monkey specimens, while the background level in noninfected specimens was very low, suggesting the usefulness of the ELISA for laboratory diagnosis with clinical specimens.

We determined the complete genome sequence of Ebola virus subtype Reston (EBO-R) in the Philippines in 1996. The deduced transcriptional signals were highly conserved among Ebola viruses except for the stop signal of L genes. The intergenic regions were composed of 4 to 7 nucleotides, and of 2 characteristic overlaps and a long intergenic region. The glycoprotein (GP) had several amino acid differences from EBO-R isolated in 1989 and 1992. The variety of GP sequences strongly suggests the independent introduction of EBO-R from unknown natural reservoirs in 1996.

Ebola (EBO) viruses were detected in specimens obtained during the hemorrhagic fever outbreak among humans in Kikwit, Democratic Republic of the Congo (DRC), in 1995 (subtype Zaire) and during an outbreak of disease in cynomolgus macaques in Alice, Texas, and the Philippines in 1996 (subtype Reston). Reverse transcriptase-polymerase chain reaction assays were developed and proven effective for detecting viral RNA in body fluids and tissues of infected individuals. Little change was seen in the nucleotide or deduced amino acid sequences of the glycoprotein (GP) of these EBO virus subtypes compared with those of their original representatives (i.e., the 1976 Yambuku, DRC, EBO isolate [subtype Zaire] and the 1989 Philippines and Reston, Virginia, isolates [subtype Reston]). The nonstructural secreted GP (SGP), the primary product of the GP gene, was more highly conserved than the structural GP, indicating different functional roles or evolutionary constraints for these proteins. Significant amounts of SGP were detected in acutely infected humans.

Ebola (subtype Reston [EBO-R]) virus infection was detected in macaques imported into the United States from the Philippines in March 1996. Studies were initiated in the Philippines to identify the source of the virus among monkey-breeding and export facilities, to establish surveillance and testing, and to assess the risk and significance of EBO-R infections in humans who work in these facilities. Over a 5-month period, acutely infected animals were found at only one facility, as determined using Ebola antigen detection. Three of 1732 monkeys and 1 of 246 animal handlers tested had detectable antibodies; all were from the same facility, which was the source of infected monkeys imported to the United States. Virus transmission, which was facilitated by poor infection-control practices, continued for several months in one facility and was stopped only when the facility was depopulated. None of the 246 employees of the facilities or 4 contacts of previously antibody-positive individuals reported an Ebola-like illness. This investigation suggests that human EBO-R infection is rare.

A mass canine rabies vaccination campaign in Sorsogon Province, the Republic of the Philippines, was conducted in April and May 1993. From 1 to 14 days following visits by vaccination teams to 30 selected villages (barangays), survey teams revisited the barangays to assess vaccine coverage. Modified cluster survey methods were used to gather information about vaccine coverage in the owned-dog population (210 households) and about characteristics of owned-dogs and factors influencing owner willingness to participate in the campaign. Vaccinated dogs were identified by asking owners about receipt of certificates given by the vaccinating teams and examining each animal for a special collar or paint mark placed on the animal at the time of vaccination. Survey results indicated that 73% (178/243) of eligible dogs were vaccinated and 82% of vaccinated dogs were marked with a collar or paint. Dogs were owned by 69% of households and ranged in age from 3 days to 13 years (median = 1 year), and the ratio of male to females dogs was 1:1. The dog-to-human ratio was 1:3.8, with an average of 1.4 dogs per household or 2.1 dogs per dog-owning household. Most dogs were kept as guards (83%) and most were free-ranging (85%). The most common reasons dogs were not vaccinated included they could not be restrained (11/64), the owner was not home (10/64), and fear of injury resulting from vaccination (10/64). The owners of 20% of vaccinated dogs reported some adverse reaction in their pet. Improved vaccine coverage was significantly associated with restrained dogs kept primarily for guard functions by owners who received information about the vaccination campaign from multiple sources. Vaccine coverage was sufficiently high to potentially control rabies transmission among dogs through herd immunity and indicated a successful vaccine campaign.

Following the detection of an Ebola-like virus in cynomolgus macaques recently imported into the United States from The Philippines, studies were initiated to document transmission at export facilities located in the latter country. At one export facility, 52.8% of 161 monkeys that died over a 2.5-month period were shown to be infected with this virus using an enzyme-linked immunosorbent assay to detect antigen in liver homogenates. A case fatality rate of 82.4% was documented for the infected monkeys. The initial anti-viral antibody prevalence among the captive macaques at this facility was 25.9% (indirect fluorescent antibody titer greater than or equal to 1:16). Followup documented infection of 24.4% of initially seronegative animals and 8.7% of initially seropositive monkeys. Being held in a gang cage versus a single cage was found to be a significant risk factor for subsequent virus infection, and the presence of IFA antibody was shown to predict protection. This study documents unequivocally for the first time the presence of an Ebola-related filovirus in Asia.