Trop. Med. Infect. Dis., Volume 2, Issue 3 (September 2017) – 29 articles

Following rabies virus (RABV) exposure, a combination of thorough wound washing, multiple-dose vaccine administration and the local infiltration of rabies immune globulin (RIG) are essential components of modern post-exposure prophylaxis (PEP). Although modern cell-culture-based rabies vaccines are increasingly used in many countries, RIG is much less available. The prohibitive cost of polyclonal serum RIG products has prompted a search for alternatives and design of anti-RABV monoclonal antibodies (MAbs) that can be manufactured on a large scale with a consistent potency and lower production costs. Robust in vitro neutralization activity has been demonstrated for the CL184 MAb cocktail, a 1:1 protein mixture of two human anti-RABV MAbs (CR57/CR4098), against a large panel of RABV isolates. In this study, we used a hamster model to evaluate the efficacy of experimental PEP against a lethal challenge. Various doses of CL184 and commercial rabies vaccine were assessed for the ability to protect against lethal infection with representatives of four distinct bat RABV lineages of public health relevance: silver-haired bat (Ln RABV); western canyon bat (Ph RABV); big brown bat (Ef-w1 RABV) and Mexican free-tailed bat RABV (Tb RABV). 42–100% of animals survived bat RABV infection when CL184 (in combination with the vaccine) was administered. A dose-response relationship was observed with decreasing doses of CL184 resulting in increasing mortality. Importantly, CL184 was highly effective in neutralizing and clearing Ph RABV in vivo, even though CR4098 does not neutralize this virus in vitro. By comparison, 19–95% survivorship was observed if human RIG (20 IU/kg) and vaccine were used following challenge with different bat viruses. Based on our results, CL184 represents an efficacious alternative for RIG. Both large-scale and lower cost production could ensure better availability and affordability of this critical life-saving biologic in rabies enzootic countries and as such, significantly contribute to the reduction of human rabies deaths globally. Full article

Residents of urban slums are at greater risk for disease than their non-slum dwelling urban counterparts. We sought to contrast the prevalences of selected non-communicable diseases (NCDs) between Brazilian adults living in a slum and the general population of the same city, by comparing the age and sex-standardized prevalences of selected NCDs from a 2010 survey in Pau da Lima, Salvador Brazil, with a 2010 national population-based telephone survey. NCD prevalences in both populations were similar for hypertension (23.6% (95% CI 20.9–26.4) and 22.9% (21.2–24.6), respectively) and for dyslipidemia (22.7% (19.8–25.5) and 21.5% (19.7–23.4)). Slum residents had higher prevalences of diabetes mellitus (10.1% (7.9–12.3)) and of overweight/obesity (46.5% (43.1–49.9)), compared to 5.2% (4.2–6.1) and 40.6% (38.5–42.8) of the general population in Salvador. Fourteen percent (14.5% (12.1–17.0)) of slum residents smoked cigarettes compared to 8.3% (7.1–9.5) of the general population in Salvador. The national telephone survey underestimated the prevalence of diabetes mellitus, overweight/obesity, and smoking in the slum population, likely in part due to differential sampling inside and outside of slums. Further research and targeted policies are needed to mitigate these inequalities, which could have significant economic and social impacts on slum residents and their communities. Full article

Risky human behavior and high density of rabies vectors in urban environments combine to increase the risk of rabies. Pet vaccination, wildlife vector management, and public health education may be the most efficient ways to prevent urban rabies epidemics. Racial, ethnic, and socio-economic factors influence the use of low-cost rabies vaccination clinics, understanding rabies reporting requirements, and learning preferences. In collaboration with the City of Greensboro and Animal Control in Guilford County, NC, we conducted a survey of rabies prevention and transmission across socio-economic strata representing Latinos, African Americans, and Whites, and different income and education levels. Compliance with vaccination was low among Latinos; African Americans and Latinos were not aware of low-cost rabies vaccination clinics; and most respondents were willing to report rabid animals but did not know whom to call. White respondents preferred online information delivery, whereas Latinos and African Americans preferred postal mail. Communication targeting the public requires the consideration of different message decoding and interpretation based on the ethnicity, income, and educational level, and other barriers such as language. Differing message delivery methods may be required to achieve full dissemination. Full article

A local study was conducted to monitor the antibiotic susceptibility of N. gonorrhoeae in Bacolod City, Philippines. A total of 88 isolates were taken during the period of 1 January 2015 to 30 June 2017, from male patients ages 12 to 72 years. The highest incidence of gonorrhea infection was in the group aged 20–24 years (34.09%). The susceptibility pattern to antibiotics was as follows: ceftriaxone 100%, cefixime 82.6%, spectinomycin 92.1%, ciprofloxacin 4.9%, tetracycline 5.1%, and penicillin G with 0%. All isolates were noted to produce beta-lactamase, which can be attributed to plasmid-mediated penicillin resistance. These findings indicate that the resistance rates of N. gonorrhoeae to most commonly-used antibiotics are increasing, and that ceftriaxone remains an effective antibiotic in treating gonorrhea infections locally. Full article

The United States Department of Agriculture (USDA), Animal and Plant Health Inspection Service (APHIS), Wildlife Services National Rabies Management Program has conducted cooperative oral rabies vaccination (ORV) programs since 1997. Understanding the eco-epidemiology of raccoon (Procyon lotor) variant rabies (raccoon rabies) is critical to successful management. Pine (Pinus spp.)-dominated landscapes generally support low relative raccoon densities that may inhibit rabies spread. However, confounding landscape features, such as wetlands and human development, represent potentially elevated risk corridors for rabies spread, possibly imperiling enhanced rabies surveillance and ORV planning. Raccoon habitat suitability in pine-dominated landscapes in Massachusetts, Florida, and Alabama was modeled by the maximum entropy (Maxent) procedure using raccoon presence, and landscape and environmental data. Replicated (n = 100/state) bootstrapped Maxent models based on raccoon sampling locations from 2012–2014 indicated that soil type was the most influential variable in Alabama (permutation importance PI = 38.3), which, based on its relation to landcover type and resource distribution and abundance, was unsurprising. Precipitation (PI = 46.9) and temperature (PI = 52.1) were the most important variables in Massachusetts and Florida, but these possibly spurious results require further investigation. The Alabama Maxent probability surface map was ingested into Circuitscape for conductance visualizations of potential areas of habitat connectivity. Incorporating these and future results into raccoon rabies containment and elimination strategies could result in significant cost-savings for rabies management here and elsewhere. Full article

This study compares data on animal rabies cases from the Chadian national rabies laboratory, hosted at the Insitut de Recherche en Elevage pour le Developpement (IRED), with bite case reporting from health facilities. The data collection accompanied a mass dog vaccination intervention over two years in N’Djaména, Chad. This allowed for a comparison of the dynamics of the incidence of animal rabies cases, human bite exposure incidence and post-exposure prophylaxis (PEP) demand during a dog rabies elimination attempt. Following the mass vaccination, the monthly animal rabies incidence dropped from 1.1/10,000 dogs, as observed prior to the campaign in 2012, to 0.061/10,000 dogs in 2014. However, the PEP demand was found to be largely unaffected. The suspicion of the rabies exposure as reported by health personnel in most cases did not reflect the status of the biting animal but rather the severity of the bite wound, resulting in inappropriate PEP recommendations. In addition, the levels of reporting dead or killed animals to the rabies laboratory was found to be very low. These results reveal a profound lack of communication between health facilities and veterinary structures and the absence of an integrated bite case management (IBCM) approach. Improved communication between human health and veterinary workers is imperative to prevent human rabies deaths through the appropriate use of PEP and to further translate success in animal rabies control into cost savings for the public health sector through a lower PEP demand. Improved training of health and veterinary personnel and the sensitisation of the public are needed to achieve good IBCM practice, to increase the rate of diagnostic testing, to provide adequate and timely PEP, and to reduce the wastage of scarce vaccine resources. Full article

Mass drug administration (MDA) for control of schistosomiasis is likely to affect transmission dynamics through a combination of passive vaccination and reduction of local transmission intensity. This is indicated in phenomenological models of immunity and the impact of MDA, yet immunity parameters in these models are not validated by empirical data that reflects protective immunity to reinfection. There is significant empirical evidence supporting the role of IgE in acquired protective immunity. This is proposed to be a form of delayed concomitant immunity, driven at least in part by protective IgE responses to the tegument allergen-like (TAL) family of proteins. Specific questions have arisen from modeling studies regarding the strength and duration of the protective immune response. At present, field studies have not been specifically designed to address these questions. There is therefore a need for field studies that are explicitly designed to capture epidemiological effects of acquired immunity to elucidate these immunological interactions. In doing so, it is important to address the discourse between theoretical modelers and immuno-epidemiologists and develop mechanistic models that empirically define immunity parameters. This is of increasing significance in a climate of potential changing transmission dynamics following long-term implementation of MDA. Full article

Efforts to eliminate the raccoon variant of the rabies virus (raccoon rabies) in the eastern United States by USDA, APHIS, Wildlife Services and cooperators have included the distribution of oral rabies vaccine baits from polyvinyl chloride (PVC) bait stations in west-central Florida from 2009 to 2015. Achieving sufficient vaccine bait uptake among urban raccoons is problematic, given limitations on aerial and vehicle-based bait distribution for safety and other reasons. One or three bait stations/km² were deployed across four 9-km² sites within rural and urban sites in Pasco and Pinellas Counties, Florida. Based on tetracycline biomarker analysis, bait uptake was only significantly different among the urban (Pinellas County) high and low bait station densities in 2012 (p = 0.0133). Significant differences in RVNA were found between the two bait station densities for both urban 2011 and 2012 samples (p = 0.0054 and p = 0.0031). Landscape differences in terms of urban structure and human population density may modify raccoon travel routes and behavior enough for these differences to emerge in highly urbanized Pinellas County, but not in rural Pasco County. The results suggest that, in urban settings, bait stations deployed at densities of >1/km² are likely to achieve higher seroprevalence as an index of population immunity critical to successful raccoon rabies control. Full article

Bait stations for distribution of oral rabies vaccine baits are designed for rabies management in highly-developed areas where traditional distribution of oral rabies vaccine baits may be difficult. As part of national efforts to contain and eliminate the raccoon (Procyon lotor) variant of the rabies virus (raccoon rabies) in the eastern United States, the United States Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services program, distributed vaccine baits by bait stations experimentally and operationally in Massachusetts during 2006-present, and in Florida during 2009–2015. In Massachusetts, a rabies virus-neutralizing antibody (RVNA) response of 42.1% for raccoons captured in areas baited with high density bait stations during 2011–2015 was achieved, compared with 46.2% in areas baited by hand, suggesting the continuation of this as a strategy for the oral rabies vaccination (ORV) program there, and for similar locations. Non-target competition for vaccine baits is problematic, regardless of distribution method. In Massachusetts, bait station visitation rates for targeted raccoons and non-target opossums (Didelphis virginiana) were similar (1.18:1) during 2006–2009 (p > 0.05). Bait station modifications for reducing non-target uptake were tested, and in Massachusetts, reduced non-target bait access was achieved with two design alternatives (p < 0.001). However, no difference was noted between the control and these two alternative designs in Florida. Due to ongoing trials of new vaccines and baits, the bait station performance of an adenovirus rabies glycoprotein recombinant vaccine bait, ONRAB^® bait (Artemis Technologies, Guelph, ON, Canada) and a vaccinia-rabies glycoprotein recombinant vaccine bait, RABORAL V-RG^®bait (Merial Limited, Athens, GA, USA), was compared. While uptake of the ONRAB bait was greater in Massachusetts (p < 0.001) in this limited trial, both types performed equally well in Florida. Since bait station tampering or theft as well as potential human bait contacts has been problematic, performance of camouflaged versus unpainted white bait stations was analyzed in terms of internal temperatures and maintaining a stable bait storage environment. In Massachusetts, camouflaged bait station interiors did not reach higher average temperatures than plain white bait stations in partially- or fully-shaded locations, while in Florida, camouflaged bait stations were significantly warmer in light exposure categories (p < 0.05). As ORV operations expand into more heavily-urbanized areas, bait stations will be increasingly important for vaccine bait distribution, and continued refinements in the strategy will be key to that success. Full article

Community engagement has become an increasingly important focus of global health programs. Arbovirus emergence in the Americas (Zika and chikungunya virues), and global goals for malaria and lymphatic filariasis elimination, mean that community-based mosquito control has taken on a new salience. But how should mosquito control initiatives be designed and implemented in ways that best engage local people? What are the challenges and trade-offs of different strategies, not only for effectiveness but also for scale-up? In this paper, we describe the social and political dynamics of a pilot study in a small town in northern Haiti. With the aim of developing a culturally-competent approach to larval source management (LSM), our pilot project combined larval surveillance with environmental management, social engagement, community education, and larvicide application. Orientated around a network of ‘Mosquito Police’ (Polisye Kont Moustik, in Haitian Creole), our approach integrated elements of formative research, social learning, and community participation. Here, we reflect on the challenges we encountered in the field, from larval mapping, staff management, education and behavior change, engagement with formal and informal leaders, and community-based environmental cleanup. We discuss how these programmatic efforts were influenced and shaped by a complex range of social, cultural, political, and economic realities, and conclude by discussing the implications of our community-based approach for the elimination of lymphatic filariasis and malaria, and other vector-borne diseases, in Haiti. Full article

In the city of Arequipa, Peru, a rabid dog was detected in March 2015, marking the reintroduction of the rabies virus in the area; more rabid dogs have been detected since then. The presence of free-roaming dogs in Arequipa seems to be higher in dry water channels, which are widespread in the city. We created a geographic information system (GIS) with surveillance data on the location of rabid dogs detected during the first year of the outbreak, as well as the water channels. We conducted a spatial analysis using Monte Carlo simulations to determine if detected rabid dogs were closer to the water channels than expected. Thirty rabid dogs were detected during the first year of the outbreak, and they were statistically associated with the water channels (average distance to closest water channel = 334 m; p-value = 0.027). Water channels might play a role in the ecology of free-roaming dog populations, functioning as ecological corridors. Landscape ecology could assist in understanding the impact of these urban structures on control activities and the persistence of transmission. Full article

Lagos bat virus (LBV) is a phylogroup II lyssavirus exclusively found in Africa. Previous studies indicated that this virus is lethal to mice after intracranial and intramuscular inoculation. The antigenic composition of LBV differs substantially from that of rabies virus (RABV) and current rabies vaccines do not provide cross protection against phylogroup II lyssaviruses. To investigate the potential role of the LBV matrix protein (M) and glycoprotein (G) in pathogenesis, reverse genetics technology was used to construct recombinant viruses. The genes encoding the glycoprotein, or the matrix and glycoprotein of the attenuated RABV strain SPBN, were replaced with those of LBV resulting in SPBN-LBVG and SPBN-LBVM-LBVG, respectively. To evaluate the immunogenicity of the LBV G, the recombinant RABV SPBNGAS-LBVG-GAS was constructed with the LBV G inserted between two mutated RABV G genes (termed GAS). All the recombinant viruses were lethal to mice after intracranial (i.c.) inoculation although the pathogenicity of SPBNGAS-LBVG-GAS was lower compared to the other recombinant viruses. Following intramuscular (i.m.) inoculation, only SPBN-LBVM-LBVG was lethal to mice, indicating that both the M and G of LBV play a role in the pathogenesis. Most interestingly, serum collected from mice that were inoculated i.m. with SPBNGAS-LBVG-GAS neutralized phylogroup I and II lyssaviruses including RABV, Duvenhage virus (DUVV), LBV, and Mokola virus (MOKV), indicating that this recombinant virus has potential to be developed as a pan-lyssavirus vaccine. Full article

More than a billion people—one-sixth of the world’s population, mostly in developing countries—are infected with one or more of the neglected tropical diseases (NTDs). Several national and international programs (e.g., the World Health Organization’s Global NTD Programs, the Centers for Disease Control and Prevention’s Global NTD Program, the United States Global Health Initiative, the United States Agency for International Development’s NTD Program, and others) are focusing on NTDs, and fighting to control or eliminate them. This review identifies the risk factors of major NTDs, and describes the global burden of the diseases in terms of disability-adjusted life years (DALYs). Full article

Rural development has been a critical component of China’s economic miracle since the start of economic reform in the early 1980s, both benefiting from and contributing to the nation’s rapid economic growth. This development has yielded substantial improvements of public health relevance, including contributing to major reductions in schistosomiasis prevalence. The history of schistosomiasis elimination in Japan suggests that development played a dominant causal role in that nation. We argue that it is highly probable that a similar story is playing out in at least some large regions of China. In particular, we summarize evidence from Sichuan Province which supports the case that economic development has led to improvements in rural irrigation and water supply which, together with changes in crop selection and agricultural mechanization, have all contributed to sustainable reductions in the prevalence of Schistosoma japonicum. The two major factors that have experienced major reductions are the area of snail habitat and the degree of human exposure, both through a variety of mechanisms which differ by region and economic circumstance. However, hotspots of transmission remain. Overall, however, economic development in traditionally endemic areas has provided the resources to carry out projects that have had major beneficial impacts on disease transmission that are likely to be sustainable. Full article

Enhanced rabies surveillance (ERS) is essential for sound oral rabies vaccination (ORV) decisions to prevent the spread of specific rabies virus variants in meso-carnivores and to achieve disease elimination. Use of a direct rapid immunohistochemistry test (dRIT) in North America for timely, accurate rabies diagnosis in the field has facilitated greater ERS emphasis since 2005. ERS used in tandem with exposure-based public health surveillance provides a comprehensive understanding of the geographic distribution of rabies as an aid to formulate effective management strategies for raccoons and other meso-carnivores. In 2015, best management practices were implemented for improving, reinvigorating, and standardizing ERS. A point system for weighing ERS sample categories was evaluated, to determine whether sampling emphasis should be focused upon ill or strange-acting animals, the highest quality category. During 2016, 70.7% of rabid animals detected through ERS in raccoon rabies management states were obtained from strange-acting animals, followed by animals found dead (14.1%), road kills (9.1%), and nuisance-collected specimens (6.1%). Sample category weights may be adjusted based on additional evaluation to ensure continued emphasis on the highest value samples. High quality ERS, in conjunction with serologic evidence of population-based immunity, form the backbone for ORV decisions in the elimination of raccoon rabies. Full article

Tungiasis is a tropical skin disease caused by the sand flea Tunga penetrans. It inflicts misery upon tens of millions of people, mostly children, across Central and South America and sub-Saharan Africa, and yet there is no globally accepted roadmap for its control. Here we review how research in the last 15 years has developed control methods and report on new grassroots and digital mapping approaches. Treatment is now possible with a two-component dimethicone, used for the treatment of headlice in Europe, Asia and Canada, but not yet available in most tungiasis-endemic areas. Prevention is possible through the daily use of repellents based on coconut oil. A Kenyan coastal community has successfully controlled tungiasis using a neem and coconut oil mix produced locally to treat cases, combined with spraying floors with neem solution and distributing closed shoes. Development of affordable hard floor technology is underway, although not yet widely available, but is a priority to control off-host stages in the floors of homes. A new web-based digital mapping application will enable researchers and health officials to collaborate, share data and map the prevalence of tungiasis. We conclude that tungiasis can be controlled through a multi-disciplinary, One Health approach. Full article

Accurate prevalence data are essential for the elimination of lymphatic filariasis (LF) as a public health problem. Despite it bearing one of the highest burdens of disease globally, there remains limited reliable information on the current epidemiology of filariasis in mainland Southeast Asia. We conducted a systematic review and meta-analysis of available literature to assess the recent and current prevalence of infection and morbidity in the region. Fifty-seven journal articles and reports containing original prevalence data were identified, including over 512,010 participants. Data were summarised using percentage prevalence estimates and a subset combined using a random effects meta-analysis by country and year. Pooled estimates for microfilaraemia, immunochromatographic card positivity and combined morbidity were 2.64%, 4.48% and 1.34% respectively. Taking into account pooled country estimates, grey literature and the quality of available data, we conclude that Lao People's Democratic Republic (PDR), Myanmar and Northeast India demonstrate ongoing evidence of LF transmission that will require multiple further rounds of mass drug administration. Bangladesh, Malaysia, Thailand and Vietnam appear close to having eliminated LF, whilst Cambodia has already achieved elimination status. We estimate that the burden of morbidity is likely high in Thailand; moderate in Cambodia, Myanmar, and Northeast India; and low in Bangladesh. There was insufficient evidence to accurately estimate the disease burden in Lao PDR, Malaysia or Vietnam. The results of this study indicate that whilst considerable progress toward LF elimination has been made, there remains a significant filariasis burden in the region. The results of this study will assist policy makers to advocate and budget for future control programs. Full article

Both cell-mediated and humoral immune effectors are important in combating rabies infection, although the humoral response receives greater attention regarding rabies prevention. The principle of preventive vaccination has been adopted for strategies of oral rabies vaccination (ORV) of wildlife reservoir populations for decades to control circulation of rabies virus in free-ranging hosts. There remains much debate about the levels of rabies antibodies (and the assays to measure them) that confer resistance to rabies virus. In this paper, data from published literature and our own unpublished animal studies on the induction of rabies binding and neutralizing antibodies following oral immunization of animals with live attenuated or recombinant rabies vaccines, are examined as correlates of protection against lethal rabies infection in captive challenge settings. Analysis of our studies suggests that, though serum neutralization test results are expected to reflect in vivo protection, the blocking enzyme linked immunosorbent assay (ELISA) result at Day 28 was a better predictor of survival. ELISA kits may have an advantage of greater precision and ability to compare results among different studies and laboratories based on the inherent standardization of the kit format. This paper examines current knowledge and study findings to guide meaningful interpretation of serology results in oral baiting monitoring. Full article

Rabies is widespread throughout Africa and Asia, despite the fact that the control and elimination of this disease has been proven to be feasible. Lesotho, a small landlocked country surrounded by South Africa, has been known to be endemic for rabies since the 1980s but the epidemiology of the disease remains poorly understood due to limited sample submission, constrained diagnostic capabilities, and a lack of molecular epidemiological data. Considering the existing challenges experienced in Lesotho, we aimed to evaluate the direct, rapid immunohistochemical test (DRIT) as an alternative to the direct fluorescent antibody (DFA) test for rabies diagnosis in Lesotho. Towards this aim, extensive training on the implementation and interpretation of the DRIT was hosted in Lesotho in April 2016 before both tests were applied to all samples subjected to routine rabies diagnosis at the Central Veterinary Laboratory (CVL). We found agreement between the DFA and DRIT assays in 90/96 samples (93.75%). The samples that produced inconsistent results (n = 6) were re-tested a further two times with both assays before being subjected to a real-time qPCR to confirm the diagnosis. Additionally, a statistically significant three-fold increase in the average number of samples submitted per month was observed after the DRIT implementation started, following continuous rabies awareness initiatives amongst the animal health professionals in the country over a 12-month period (p = 0.0279). Partial G-L intergenic regions of selected rabies-positive samples (n = 21) were amplified, sequenced, and subjected to phylogenetic analyses. Molecular epidemiological analyses, that included viruses from neighbouring provinces in South Africa, suggested that at least three independent rabies cycles within Lesotho were implicated in instances of cross-border transmission. This study has evaluated alternative methods for diagnosing and improving rabies surveillance in Lesotho, as well as providing new information that would be of importance in the planning of future disease intervention campaigns, not only in Lesotho, but also in neighbouring South Africa. Full article

Abstract: International rabies networks have been formed in many of the canine-rabies endemic regions around the world to create unified and directed regional approaches towards elimination. The aim of the first sub-regional Eastern Africa rabies network meeting, which included Kenya, Ethiopia, Tanzania, Rwanda, and Uganda, was to discuss how individual country strategies could be coordinated to address the unique challenges that are faced within the network. The Stepwise Approach towards Rabies Elimination and the Global Dog Rabies Elimination Pathway tool were used to stimulate discussion and planning to achieve the elimination of canine-mediated human rabies by 2030. Our analysis estimated a total dog population of 18.3 million dogs in the Eastern Africa region. The current dog vaccination coverage was estimated to be approximately 5% (915,000 dogs), with an estimated 4910 vaccinators available. Assuming that every vaccinator performs rabies vaccination, this equated to each vaccinator currently vaccinating 186 dogs per year, whilst the target would be to vaccinate 2609 dogs every year for the community to reach 70% coverage. In order to achieve the World Health Organization-recommended 70% vaccination coverage, an additional 11 million dogs need to be vaccinated each year, pointing to an average annual shortfall of $ 23 million USD in current spending to achieve elimination by 2030 across the region. Improved vaccination efficiency within the region could be achieved by improving logistics and/or incorporating multiple vaccination methods to increase vaccinator efficiency, and could serve to reduce the financial burden associated with rabies elimination. Regional approaches to rabies control are of value, as neighboring countries can share their unique challenges while, at the same time, common approaches can be developed and resource-saving strategies can be implemented. Full article

Over five years, a total of 646 P. aeruginosa isolates was acquired from different clinical specimens and their resistance to the commonly used anti-pseudomonal antibiotics was determined. The majority of the isolates were from respiratory (60.99%) and urinary sources (23.22%) while the least came from transudates and exudates (2.01%). Most of the samples were acquired from older adults (77.55%), most of whom were admitted (67.03%). Amikacin was found to be the most effective drug with a resistance rate of 7.5%, followed by piperacillin/tazobactam (8.5%) and gentamicin (13.5%). On the other hand, 26.7% of the isolates were resistant to levofloxacin. Almost 100% of the isolates were screened positive for AmpC production, which may suggest inducible resistance against expanded spectrum beta-lactamase. Furthermore, for the last three years, P. aeruginosa isolates from this area have been noted to have decreasing resistance only to aztreonam and gentamicin. Also, for five years, a mean MAR index of 0.17 was noted which indicates either proper antibiotic use or most isolates did not come from high-risk areas. Moreover, there was no significant difference in the resistance of P. aeruginosa when compared by specimen source (p = 0.662), but significant when compared by year band (p = 0.02). Full article

Vampire bat-transmitted rabies was first recognized in Trinidad during a major outbreak reported in 1925. Trinidad is the only Caribbean island with vampire bat-transmitted rabies. We conducted a literature review to describe the changing epidemiology of rabies in Trinidad and give a historical perspective to rabies prevention and control measures on the island. The last human case of rabies occurred in 1937 and although no case of canine-transmitted rabies was reported since 1914, sporadic outbreaks of bat-transmitted rabies still occur in livestock to date. Over the last century, seven notable epidemics were recorded in Trinidad with the loss of over 3000 animals. During the 1950s, several measures were effectively adopted for the prevention and control of the disease which led to a significant reduction in the number of cases. These measures include: vampire bat population control, livestock vaccination, and animal surveillance. However, due to lapses in these measures over the years (e.g., periods of limited vampire control and incomplete herd vaccination), epidemics have occurred. In light of the significant negative impact of rabies on animal production and human health, rabies surveillance in Trinidad should be enhanced and cases evaluated towards the design and implementation of more evidence-based prevention and control programs. Full article

The aetiological agent of rabies is a member of the Lyssavirus genus (Rhabdoviridae family, order Mononegavirales). The disease (rabies) is endemic in many parts of Asia and Africa and still remains an important public and veterinary health threat. In Nigeria, there is a dearth of information on the natural infection and/or exposure of bat species to lyssaviruses. Therefore, this study was undertaken to assess the prevalence of rabies virus (RABV) neutralizing antibodies in sera obtained from bats from the central Plateau and North-East Bauchi States in Nigeria. Two hundred serum samples were collected from Nigerian fruit bats from six different locations and tested for anti-RABV antibodies using a commercial blocking ELISA. Of the 200 bat serum samples collected, one batch consisting of 111 samples did not meet the validation criteria and hence was not included in the final analysis. Of the remaining 89, only three (3.4%) contained anti-lyssavirus antibodies, demonstrating a low prevalence of lyssavirus antibodies in the study population. In order to further understand the exposure of bat species to phylogroup II lyssaviruses (Lagos bat virus and Mokola virus), the same panel of samples will be tested for neutralizing antibodies to phylogroup II members, viruses that do not cross-neutralize with members of phylogroup I. Full article

Bats are key species for ecological function, but they are also reservoirs of zoonotic agents, such as lyssaviruses that cause rabies. Little is known about the maintenance and transmission of lyssaviruses in bats, although the observation of clinically sick bats, both in experimental studies and wild bats, has at least demonstrated that lyssaviruses are capable of causing clinical disease in bat species. Despite this, extensive surveillance for diseased bats has not yielded lyssaviruses, whilst serological surveys demonstrate that bats must be exposed to lyssavirus without developing clinical disease. We hypothesize that there is endemic circulation of Lagos bat virus (LBV) in the straw-coloured fruit bat (Eidolon helvum) in Ghana, West Africa. To investigate this further, longitudinal blood sampling was undertaken quarterly between 2012 and 2014 on wild E. helvum at two sites in Ghana. Serum samples were collected and tested for LBV-neutralizing antibodies using a modified flourescent antibody virus neutralisation (FAVN) assay (n = 294) and brains from moribund or dead bats were tested for antigen and viral RNA (n = 55). Overall, 44.7% of the 304 bats sampled had LBV-neutralising antibodies. None of the brain samples from bats contained lyssavirus antigen or RNA. Together with the results of an earlier serological study, our findings demonstrate that LBV is endemic and circulates within E. helvum in Ghana even though the detection of viral infection in dead bats was unsuccessful. Confirmation that LBV infection is endemic in E. helvum in Ghana is an important finding and indicates that the potential public health threats from LBV warrant further investigation. Full article

The rapid fluorescent focus inhibition test (RFFIT) is routinely used in the United States to measure rabies virus neutralizing antibodies (rVNA). RFFIT has a long history of reproducible and reliable results. The test has been modified over the years to use smaller volumes of reagents and samples, but requires a 50 μL minimum volume of test serum. To conduct pathogenesis studies, small laboratory animals such as mice are regularly tested for rVNA, but the minimum volume for a standard RFFIT may be impossible to obtain, particularly in scenarios of repeated sampling. To address this problem, a micro-neutralization test was developed previously. In the current study, the micro-neutralization test was compared to the RFFIT using 129 mouse serum samples from rabies vaccine studies. Using a cut-off value of 0.1 IU/mL, the sensitivity, specificity, and concordance of the micro-neutralization test were 100%, 97.5%, and 98%, respectively. The geometric mean titer of all samples above the cut-off was 2.0 IU/mL using RFFIT and 3.4 IU/mL using the micro-neutralization test, indicating that titers determined using the micro-neutralization test are not equivalent to RFFIT titers. Based on four rVNA-positive hamster serum samples, the intra-assay coefficient of variability was 24% and inter-assay coefficient of variability was 30.4%. These results support continued use of the micro-neutralization test to determine rabies virus neutralizing antibody titers for low-volume serum samples. Full article

Asian countries bear the greatest burden of the disease, with a majority (59%) of rabies-related deaths occurring in Asia. In order to promote best practices, we summarized national human vaccination guidelines across this region, to highlight differences and similarities and to discuss the aspects that would benefit from updates. National management guidelines for rabies were retrieved from various sources to extract information on rabies pre- and post-exposure prophylaxis (PrEP, and PEP), booster vaccination, and route of administration. Rabies guidelines recommendations for wound management and PrEP across Asia are broadly aligned to the World Health Organization (WHO) guidelines. For PEP, the 5-dose Essen, and the 4-dose Zagreb are the regimens of choice for intramuscular (IM), and the Thai Red Cross regimen for intradermal (ID), administration. Several national guidelines have yet to endorse ID vaccine administration. Most guidelines recommend rabies immunoglobulin in category III exposures. Booster recommendations are not included in all guidelines, with limited clarity on booster requirement across the spectrum of risk of rabies exposure. In conclusion, national recommendations across Asian countries differ and while some guidelines are closely aligned to the WHO recommendations, resource-saving ID administration and use of rational abbreviated schedules have yet to be endorsed. Full article

Rabies remains a major public health issue worldwide, especially in developing countries where access to medical care can represent a real challenge. While there is still no cure for rabies, it is a vaccine-preventable disease with pre- and post-exposure prophylaxis regimens approved by the World Health Organization (WHO). However, many rabies-exposed individuals have limited access to vaccines and virus-neutralizing antibodies approved for post-exposure prophylaxis. Unfortunately, any delay in the administration of these reagents can have lethal consequences. This highlights the need to develop cost-effective immunological reagents with a greater window of efficacy. Live-attenuated vaccine strains of rabies virus presents a potential treatment in filling this gap. We show here that immunization with live-attenuated vaccines provide long-lasting rabies immunity, superior to the protection induced by inactivated vaccines. In the absence of an immunostimulatory adjuvant, vaccination with multiple doses of inactivated rabies virus induces a type-2 immune response. This type of immunity is highly effective at inducing neutralizing antibody but has limited efficacy in clearing the virus from central nervous system (CNS) tissues. In contrast, a single infection with live-attenuated rabies vaccine safely drives a type-1 immune response, associated with both the production of a neutralizing antibody and the clearance of wild-type rabies virus from CNS tissues. These results indicate that live-attenuated rabies strains have the potential to be more effective in post-exposure prophylaxis than conventional inactivated vaccines. Full article

Following an incursion of the mid-Atlantic raccoon variant of the rabies virus into southern Ontario, Canada, in late 2015, the direct rapid immunohistochemical test for rabies (dRIT) was employed on a large scale to establish the outbreak perimeter and to diagnose specific cases to inform rabies control management actions. In a 17-month period, 5800 wildlife carcasses were tested using the dRIT, of which 307 were identified as rabid. When compared with the gold standard fluorescent antibody test (FAT), the dRIT was found to have a sensitivity of 100% and a specificity of 98.2%. Positive and negative test agreement was shown to be 98.3% and 99.1%, respectively, with an overall test agreement of 98.8%. The average cost to test a sample was $3.13 CAD for materials, and hands-on technical time to complete the test is estimated at 0.55 h. The dRIT procedure was found to be accurate, fast, inexpensive, easy to learn and perform, and an excellent tool for monitoring the progression of a wildlife rabies incursion. Full article

During the endgame of elimination programs, parasite populations may exhibit dynamical phenomena not typical of endemic disease. Particularly, monitoring programs for tracking infection prevalence may be hampered by overall rarity, the sporadic and unpredictable timing and location of outbreaks, and under-reporting. A particularly important problem for monitoring is determining the distance that must be covered to achieve the elimination threshold at an effective reproduction number less than one. In this perspective, we suggest that this problem may be overcome by measuring critical slowing down. Critical slowing down is a phenomenon exhibited by nonlinear dynamical systems in the vicinity of a critical threshold. In infectious disease dynamics, critical slowing down is expressed as an increase in the coefficient of variation and other properties of the fluctuations in the number of cases. In simulations, we show the coefficient of variation to be insensitive to under-reporting error and therefore a robust measurement of the approach to elimination. Additionally, we show that there is an inevitable delay between the time at which the effective reproduction number is reduced to below one and complete elimination is achieved. We urge that monitoring programs include dynamical properties such as critical slowing down in their metrics for measuring achievement and avoid withdrawing control activities prematurely. Full article