14/05/2018
PAKET INFORMASI PERPUSTAKAAN BBLITVET
NO.2, 2018
BRUCELOSIS
1. Abdelbaset, A. E., Abushahba, M. F. N., Hamed, M. I., & Rawy, M. S. (2018). Sero-diagnosis of brucellosis in sheep and humans in Assiut and El-Minya governorates, Egypt. International Journal of Veterinary Science and Medicine, (September 2017), 0–1. https://doi.org/10.1016/J.IJVSM.2018.01.007
Abstract
Egypt is an endemic area with brucellosis, so wherever herd problem associated abortion is present, brucellosis should be suspected, and its sero-diagnosis is needed. The present study aimed to estimate the seroprevalence of brucellosis in sheep and their contact humans in Assiut and El-Minya Governorates where a history of abortion in sheep was the chief complaint of the farmers; besides; the appearance of signs of undulant fever among some contact humans. Also, to identify the risk factors for brucellosis seropositivity at human and animal level. Serum samples were collected from 189 sheep and 53 in contact humans in Assiut and El-Minya Governorates, Egypt, during 2017. Antibodies against brucellosis were measured in the serum samples using Rose Bengal Plate test (RBPT) and were further confirmed using Serum Tube Agglutination Test (STAT). The overall seroprevalence ofbrucellosis using RBPT was 15.87% in sheep and that in humans was 9.44% (5 of 53), respectively. STAT confirmed that 40% of the RBPT-positive reactor sheep were infected by Brucella abortus, 16.67% were containing Brucella melitensis and 20% were experiencing a mixed infection of both Br. abortus and Br. melitensis. Additionally, 80% of the RBPT-positive reactor humans were infected with Br. abortus only and 20% were having both species of Brucella. Among different analyzed variables in this study, the age and farming system of the examined sheep were statistically significant. There was no significant effect in relation to gender, abortion history and pregnancy status of the examined animals, however, higher exposure rates were found among males, abortive animals, and recently calved animals. Gender of the tested humans and presence of seropositive sheep in contact differed significantly in acquiring the infection. Nevertheless, other factors, including age, education, and profession were statistically insignificant on getting human brucellosis. These results indicate the high seroprevalence of brucellosis in humans and sheep in the study areas and generally in Egypt, and therefore, control programs should be implemented.
2. Ning, C., Shuyi, G., Tao, Y., Hao, Z., & Zhang, X. (2018). Epidemiological survey of human brucellosis in Inner Mongolia, China, 2010–2014: A high risk groups-based survey. Journal of Infection and Public Health, 11(1), 24–29.
https://doi.org/10.1016/j.jiph.2017.02.013
Abstract
Brucellosis, a zoonosis which can seriously harm public health. Inner Mongolia is known as an endemic region of human brucellosis in China. The aim of this study is to present the epidemic of human brucellosis in Inner Mongolia from 2010 to 2014, and to provide the evidence of preventing from brucellosis in endemic areas. The study included 838,956 participants by cluster random sampling from 2010 to 2014. The contents of this study included questionnaire survey and serological testing. The seropositive rate was calculated based on the serological testing results, tested to determine whether the participants were infected by brucellosis. The new brucellosis cases were diagnosed using the questionnaire data and serological testing results then and the incidence rate was obtained. We also plotted spatial distribution maps based on the seropositive and incidence rate of human brucellosis. The total seropositive and incidence rate of human brucellosis among the high risk groups in Inner Mongolia from 2010 to 2014 was 35.91‰ and 18.25‰ respectively. The epidemic of the mid-eastern Inner Mongolia was decreased, however, the epidemic has worsened in western Inner Mongolia. Despite the epidemic of human brucellosis among the high risk groups of Inner Mongolia decreased significantly from 2010 to 2014, increased prevention and control measures are urgently needed.
3. López, G. E., Peña, S., Escobar, G. I., Hasan, D. B., & Lucero, N. E. (2018). Serological study of brucellosis in Argentine Creole sheep. Revista Argentina de Microbiologia, (xx). https://doi.org/10.1016/j.ram.2017.08.004
Abstract
Ovine cattle was introduced into America during the Spanish conquest with the second journey of Columbus to the Antilles and was disseminated throughout the region. In 1587, sheep were introduced into Argentina, later developing into the "Creole" breed. We selected 486 animals from different Argentine provinces with the aim of determining the serological status of brucellosis caused by Brucella melitensis and Brucella ovis. For the detection of antibodies against smooth Brucella spp., the Rose Bengal test (RBT) was performed as screening test while the serum agglutination test (SAT) and 2 mercapto-ethanol (2ME) were run as a confirmatory technique. Moreover, for the detection of antibodies against rough Brucella spp., we used the rapid slide agglutination test (RSAT) for screening and an indirect ELISA (IELISA) as confirmatory assay. This study showed that the total positive percentage of brucellosis due to B. ovis was 2.9%. Excluding the animals mixed with the Suffolk breed; seropositivity would be 0.6%. All animals tested negative for brucellosis caused by B. melitensis.
4. Khamassi Khbou, M., Htira, S., Harabech, K., & Benzarti, M. (2018). First case-control study of zoonotic brucellosis in Gafsa district, Southwest Tunisia. One Health, 5(December 2017), 21–26. https://doi.org/10.1016/j.onehlt.2017.12.001
Abstract
A case-control study was conducted, aimed to describe the clinical human brucellosis (CHB) pattern during 2015 in the Gafsa region (Southwest Tunisia) and to investigate the main risk factors involved in the disease occurrence. One hundred and four CHB cases were notified in 2015 in Gafsa district. All CHB cases that own ruminants were contacted, but only 32 accepted to participate in a matched case-control study. Thirty-two and thirty-one CHB cases and controls, respectively, were included in the study. The subjects were interviewed using a structured questionnaire. A total of 662 domestic ruminants (cattle, sheep and goats) belonging to cases and controls, were screened using the Rose Bengal Test, as recommended by the World Organisation of Animal Health. During 2015, the incidence of CHB was estimated to 30.8 per 100,000 inhabitants affecting mainly males aged between 30 and 39 years. The overall animal seropositivity to Brucella, was 21 and 1.9% in case and control farms, respectively (p < 0.0001). Only five risk factors were found to be significant: overall animal seropositivity (OR = 65.2; 95%CI: 13.3–318.7); handling aborted females (OR = 43.1; 95%CI: 8.3–222.7); presence of male ruminants in the herds (OR = 18.5; 95%CI: 5.18–66); owning seropositive goats (OR = 18.3; 95%CI: 2.4–137.6), owning seropositive sheep (OR = 9.66; 95%CI: 2.9–31.5) and history of abortion during the previous year in the herd (OR = 4.6; 95%CI: 1.3–12.6). Vaccination of animals against brucellosis was associated with lower odds of human brucellosis (OR = 0.03; 95%CI: 0.004–0.2). Raw milk and derivatives consumption was not a risk factor of human brucellosis. Based on this study, ruminants' vaccination coverage should be increased by enhancing the number of vaccinated animals and systematically including male ruminants in Tunisia. Comprehensive education programmes targeting both farmers and general population should be implemented.
5. Sagamiko, F. D., Muma, J. B., Karimuribo, E. D., Mwanza, A. M., Sindato, C., & Hang’ombe, B. M. (2018). Sero-prevalence of Bovine Brucellosis and associated risk factors in mbeya region, Southern highlands of Tanzania. Acta Tropica, 178(November 2017), 169–175. https://doi.org/10.1016/j.actatropica.2017.11.022
Abstract
A cross-sectional study was conducted to establish the seroprevalence of brucellosis and associated risk factors in indigenous and exotic breeds of cattle from 178 farms in Mbeya region. A total of 1211 cattle (929exotic cattle from 108 commercial farms and 282 indigenous cattle from 70 traditional farms) were tested for Brucella antibodies using the Rose Bengal Plate Test (RBPT) and competitive Enzyme Linked Immunosorbent Assay (c-ELISA) as screening and confirmatory tests, respectively. The overall animal-level seroprevalence was 9.3%; 11.3% (95% CI: 9.4–13.5) in indigenous cattle and 2.8% (95% CI:1.4–5.6) in exotic cattle. Further, the overall herd level seroprevalence was 32.0%; 50.5% (95% CI: 40.9–59.9) in indigenous cattle and 4.2% (95% CI: 1.3–12.4) in exotic cattle. Infections were higher in cattle aged 6–10 years old, (39.8%; 95% CI: 31.2–49.1) followed by those aged 1–5 years (5.8%; 95% CI: 4.8–6.6) and 11–15years old (2.7%; 95% CI: 0.8–8). When compared to cattle sampled from herds size of 1–50, those sampled from the herd sizes of 51–100 and 101–150 had higher odds of brucellosis seropositivity [(OR = 3.6, CI: 1.76–7.16, p < 0.001) and (OR = 3.0, CI: 1.09–8.04, p = 0.033). The odds of seropositivity in animals which calved on pasture was 3.0 (CI: 1.1–7.8, p = 0.028) compared to those that calved at home. Brucella seroprevalence was also observed to vary according to districts, with Mbarari district recording the highest (45.4%). It is evident from the study that Brucellosis is present in Mbarari, Mbeya and Momba districts of Mbeya Region. The findings of this study provide some baseline data that could contribute to the design and implementation of brucellosis control measures in the study areas.
6. Bastos, C. R., Mathias, L. A., Jusi, M. M. G., Santos, R. F. Dos, Silva, G. C. P. da, Andre, M. R., … Burger, K. P. (2018). Evaluation of dot-blot test for serological diagnosis of bovine brucellosis. Brazilian Journal of Microbiology : [Publication of the Brazilian Society for Microbiology], 1–5.
https://doi.org/10.1016/j.bjm.2017.10.002
Abstract
The objective of this study was to standardize and validate the dot-blot test for the serological diagnosis of bovine brucellosis, compare the results with those found in the 2-mercaptoethanol (2-ME) and complement fixation test (CF), and estimate the relative sen- sitivity and specificity of the dot-blot compared to these tests. Fifty bovine blood serum samples were used for the test standardization, and 1315 samples were used for evaluation and comparison between the tests; the results were compared using the Kappa indicator. At the end of standardization, it was established as optimal for the antigen obtained from Bru- cella abortus B19 after passing through a microorganism rupture process, the blood serum samples diluted at 1:100, and the conjugate at 1:30,000. The comparison of the dot-blot results with 2-ME showed Kappa index of 0.9939, sensitivity of 99.48%, and specificity 99.91%, with CF, Kappa index of 0.8226, sensitivity 100% and specificity 95.32%. Using the combination of the test results 2-ME and CF to establish the true condition of the animal, the dot-blot showed relative sensitivity of 100%, and relative specificity of 99.91%. The evaluated test proved to be effective and reliable, besides being easy to handle and interpret the results. © 2018 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. This is
7. Köse, Ş. ̧, Kiliç, S., & Özbel, Y. (2005). Identification of Brucella species isolated from proven brucellosis patients in Izmir, Turkey. Journal of Basic Microbiology, 45(4), 323–327. https://doi.org/10.1002/jobm.200410469
ABSTRACT
In many parts of the world, brucellosis has significantly decreased, but it is still a problem in some regions of Turkey. Totally, 11 Brucella strains isolated from the blood cultures of patients with presumptive diagnosis of brucellosis were identified to species and biovar level. For species identification, (i) CO2 requirements of isolates; (ii) detection of urease activation; (iii) detection of H2S production; (iv) dye sensitivities (thionine and basic fuchsin); (v) susceptibility to Brucella phage and (vi) agglutination with monospecific antisera (A and M) were performed. Ten out of 11 isolates were identified as B. melitensis biovar 3 and one out of 11 were identified as B. melitensis biovar 1. The sensitivity of isolates to antibiotics was determined by the E-test. All isolates were found to be sensitive to doxycycline, rifampin, ciprofloxacin and cephtriaxone. Only one out of 11 isolates was found to be semi-sensitive to trimethoprim/sulfamethoxazole (cotrimoxazole).
LEPTOSPIROSIS
8. Garshasbi, V., Naddaf, S. R., Aghighi, Z., Hassan, N., Pooya, M., & Mostafavi, E. (2018). Leptospirosis in Caspian Sea littoral, Gilan Province, Iran. Acta Tropica, 181(January 2017), 11–15. https://doi.org/10.1016/j.actatropica.2018.01.010
Abstract
In Iran, leptospirosis is endemic to Caspian Sea littoral. The disease appears as a seasonal infection mostly affecting people in rural areas involved in farming. We investigated the prevalence of this infection among suspected patients in Gilan Province by an indirect immunofluorescent assay (IFA), and two PCR protocols, a nested-PCR and a real-time PCR (qPCR), targeting rrs and lipL32 genes, respectively. We also identified the common Leptospira species by sequencing a partial sequence of rrs gene. Out of the 128 sera examined by IFA, 25.78% were positive with the antibody titers ≥1/80. The antibody titer in 39.06% of sera ranged from 1/10 to 1/140, and 35. 16% showed no antibodies, all considered negative. Nested PCR and qPCR detected Leptospira DNA in 20.31% and 18.75% of the sera, respectively. The two PCR assays had 98.43% agreement (K = 0.93) and showed an inverse correlation with the IFA titers. Also, three pathogenic Leptospira species, L. kirschneri (n = 10), L. introgans (n = 8), and L. borgpetersenii (n = 2) were identified from the clinical specimens in the study area. In our hands both PCR assays proved very efficient for early diagnosis of illness and could be used in combination with IFA for both diagnosis and epidemiological studies, but nested PCR was cheaper and appeared more appropriate for our laboratories in rural settings.
9. Penna, B., Marassi, C. D., Libonati, H., Narduche, L., Lilenbaum, W., & Bourhy, P. (2017). Diagnostic accuracy of an in-house ELISA using the intermediate species Leptospira fainei as antigen for diagnosis of acute leptospirosis in dogs. Comparative Immunology, Microbiology and Infectious Diseases, 50, 13–15. https://doi.org/10.1016/j.cimid.2016.11.004
Abstract
Diagnosis of animal leptospirosis is still challenging. The microscopic agglutination test, is the current method for diagnosing leptospirosis. However, this technique requires specific equipment, highly trained staff and the maintenance of live cultures of several reference strains of Leptospira for use as antigens. Recently, an ELISA (enzyme-linked immunosorbent assay) employing a Leptospira fainei serovar Hurstbridge based antigen for the early diagnostic of human leptospirosis was developed. In this study we estimate the diagnostic sensitivity and specificity of this test in identifying acute canine leptospirosis. A total of 271 serum samples divided into five panels and tested by MAT as a reference test, were used to evaluate the ELISA. Comparing acutely and non-acutely infected dogs, ELISA-Hb showed 95.6% sensitivity and 93% specificity. L. fainei-based ELISA is adequate for diagnosing acute canine leptospirosis, with high sensitivity and specificity and presenting practical advantages when compared to current techniques.
10. Jiménez, J. I. S., Marroquin, J. L. H., Richards, G. A., & Amin, P. (2018). Leptospirosis: Report from the task force on tropical diseases by the World Federation of Societies of Intensive and Critical Care Medicine. Journal of Critical Care, 43, 361–365. https://doi.org/10.1016/j.jcrc.2017.11.005
Abstract
Leptospirosis is a zoonosis caused by a gram negative aerobic spirochete of the genus Leptospira. It is acquired by contact with urine or reproductive fluids from infected animals, or by inoculation from contaminated water or soil. The disease has a global distribution, mainly in tropical and subtropical regions that have a humid, rainy climate and is also common in travelers returning from these regions. Clinical suspicion is critical for the diagnosis and it should be included in the differential diagnosis of any patient with a febrile hepatorenal syndrome in, or returning from endemic regions. The leptospiremic phase occurs early and thereafter there is an immunologic phase in which the most severe form, Weil's disease, occurs. In the latter, multiple organ dysfunction predominates. The appropriate diagnostic test depends on the stage of the disease and consists of direct and indirect detection methods and cultures. Severely ill patients need to be monitored in an ICU with appropriate anti-bacterial agents and early, aggressive and effective organ support. Antibiotic therapy consists of penicillins, macrolides or third generation cephalosporins.
11. Santos, J. V., Pereira, P. R. M., Fernandes, L. G. V., Siqueira, G. H., de Souza, G. O., Souza Filho, A., … Nascimento, A. L. T. O. (2017). Binding of human plasminogen by the lipoprotein LipL46 of Leptospira interrogans. Molecular and Cellular Probes, (October), 0–1. https://doi.org/10.1016/j.mcp.2017.10.004
Abstract
Leptospirosis is a widespread zoonosis caused by pathogenic Leptospira. Bacteria disseminate via the bloodstream and colonize the renal tubules of reservoir hosts. Leptospiral surface-exposed proteins are important targets, because due to their location they can elicit immune response and mediate adhesion and invasion processes. LipL46 has been previously reported to be located at the leptospiral outer membrane and recognized by antibodies present in serum of infected hamsters. In this study, we have confirmed the cellular location of this protein by immunofluorescence and FACS. We have cloned and expressed the recombinant protein LipL46 in its soluble form. LipL46 was recognized by confirmed leptospirosis human serum, suggesting its expression during infection. Binding screening of LipL46 with extracellular matrix (ECM) and plasma components showed that this protein interacts with plasminogen. The binding is dose-dependent on protein concentration, but saturation was not reached with the range of protein concentration used. Kringle domains of plasminogen and lysine residues of the recombinant protein are involved in the binding because the lysine analog, amino caproic acid (ACA) almost totally inhibited the reaction. The interaction of LipL46 with plasminogen generates plasmin in the presence of plasminogen activator uPA. Because plasmin generated at the leptospiral surface can degrade ECM molecules and decrease opsonophagocytosis, we tentatively infer that Lip46 has a role in helping the invasion process of pathogenic Leptospira.
12. Olmo, L., Dye, M. T., Reichel, M. P., Young, J. R., Nampanya, S., Khounsy, S., … Bush, R. D. (2018). Investigation of infectious reproductive pathogens of large ruminants: Are neosporosis, brucellosis, leptospirosis and BVDV of relevance in Lao PDR? Acta Tropica, 177(July 2017), 118–126. https://doi.org/10.1016/j.actatropica.2017.10.007
Abstract
N. caninum, bovine viral diarrhoea virus, Brucella abortus and Leptospira interrogans serovar Hardjo are globally significant reproductive pathogens that cause abortion and reproductive loss in large ruminants. Prevalence information is lacking in Lao People's Democratic Republic (Laos) despite the poor reproductive performance of cattle and buffalo. Serological examination of frozen cattle (n = 90) and buffalo (n = 61) sera by commercially available enzyme-linked immunosorbent assays provided the first reported screening of some of these pathogens in Laos. Seroprevalence differed amongst these large ruminant species, with N. caninum, BVDV and L. interrogans serovar Hardjo antibodies found in 68.9% (95% CI ± 11.6), 4.9% (95% CI ± 5.4) and 3.3% (95% CI ± 4.5) of buffalo sera, respectively, and in 7.8% (95% CI ± 5.5), 10.0% (95% CI ± 6.2) and 22.2% (95% CI ± 8.6) of cattle sera, respectively. Buffalo sera had a significantly higher seroprevalence of N. caninum compared to cattle (p < 0.001) and cattle sera had a significantly higher seroprevalence of L. interrogans serovar Hardjo compared to buffalo (p = 0.003). Variability was also observed across provinces for N. caninum in buffalo (p = 0.007) and for L. interrogans serovar Hardjo in cattle (p = 0.071), suggesting provincial risk factors conducive to pathogen transmission. BVDV and N. caninum seropositivity were negatively associated in buffalo (p = 0.018) and cattle (p = 0.003). In buffalo, L. interrogans serovar Hardjo and BVDV seropositivity were associated (p = 0.035, p = 0.039). The identification of antibodies against three major abortifacient pathogens in Laos prompts further research to determine if infection is associated with low reproductive efficiency and the risk factors for infection. This is needed for the development of evidence based prevention strategies for improved large ruminant reproductive management among smallholders in Laos.
13. Acevedo-Whitehouse, K., Gulland, F. M. D., & Bowen, L. (2018). MHC class II DRB diversity predicts antigen recognition and is associated with disease severity in California sea lions naturally infected with Leptospira interrogans. Infection, Genetics and Evolution, 57(November 2017), 158–165. https://doi.org/10.1016/j.meegid.2017.11.023
Abstract
We examined the associations between California sea lion MHC class II DRB (Zaca-DRB) configuration and diversity, and leptospirosis. As Zaca-DRB gene sequences are involved with antigen presentation of bacteria and other extracellular pathogens, we predicted that they would play a role in determining responses to these pathogenic spirochaetes. Specifically, we investigated whether Zaca-DRB diversity (number of genes) and configuration (presence of specific genes) explained differences in disease severity, and whether higher levels of Zaca-DRB diversity predicted the number of specific Leptospira interrogans serovars that a sea lion's serum would react against. We found that serum from diseased sea lions with more Zaca-DRB loci reacted against a wider array of serovars. Specific Zaca-DRB loci were linked to reactions with particular serovars. Interestingly, sea lions with clinical manifestation of leptospirosis that had higher numbers of Zaca-DRB loci were less likely to recover from disease than those with lower diversity, and those that harboured Zaca-DRB.C or –G were 4.5 to 5.3 times more likely to die from leptospirosis, regardless of the infective serovars. We propose that for leptospirosis, a disadvantage of having a wider range of antigen presentation might be increased disease severity due to immunopathology. Ours is the first study to examine the importance of Zaca-DRB diversity for antigen detection and disease severity following natural exposure to infective leptospires.
RABIES
14. Sirikun, J., Suputtamongkol, Y., Rattanachinakorn, P., & Primsirikunawut, A. (2018). Immunogenic response in obese patients undergoing rabies post-exposure prophylaxis with combined equine rabies immunoglobulin and rabies vaccination. Vaccine, 36(2), 285–291. https://doi.org/10.1016/j.vaccine.2017.11.058
Abstract
Background Obesity is a risk factor for increased morbidity and mortality associated with many vaccine preventable infectious diseases such as influenza. Moreover, higher volume of passive rabies immunoglobulin (RIG) due to weight based dosing might suppress vaccine-induced immune responses in obese patients. This study aimed to evaluate the effect of obesity on humoral immune responses to combined equine RIG and rabies vaccine treatment among patients with WHO category III exposure to a rabies suspected animal. Methods A single centre, prospective, open-labelled study among WHO category III rabies exposed patients was conducted to compare serum rabies virus neutralizing antibody (RVNA) responses measured by rapid fluorescent focus inhibition test between obese (body mass index, BMI > 30 kg/m2) and control (BMI < 25 kg/m2) patients after combined immunization with equine rabies immunoglobulin and purified chick-embryo cell rabies vaccine for post exposure prophylaxis treatment. Results Post-vaccination geometric mean titer (GMT) of RVNA concentrations between two groups at day 7 were 0.33 (95% CI: 0.23, 0.46) vs 0.39 (95% CI: 0.27, 0.55), 4.61 (95% CI: 3.20, 6.63) vs 3.78 (95% CI: 2.77, 5.16) at day 14, and 7.45 (95% CI: 5.86, 9.49) vs 5.93 (95%CI: 4.46–7.90) at day 28 for obese and control patients, respectively. There was no statistically significant difference of RVNA GMT between two groups. Seroconversion to at least adequate concentration (RVNA titer ≥0.5 IU/mL) rates were 34% at day 7 and 100% at days 14 and 28 in both groups. There were no immediate hypersensitivity reaction and no serious adverse events observed during the study period. Conclusions There was no evidence of immunosuppression of antibodies’ responses in obese patients. Combined ERIG and rabies virus vaccination for post exposure treatment is safe.
15. Wade, L. L. (2018). Vaccination of Ferrets for Rabies and Distemper. Veterinary Clinics of North America - Exotic Animal Practice, 21(1), 105–114. https://doi.org/10.1016/j.cvex.2017.08.004
Abstract
Companion ferrets need to be vaccinated against 2 viral diseases that cause neurologic illness: canine distemper and rabies. Although not common in ferrets, both viruses are fatal in ferrets and rabies virus is also fatal in humans. In this article, we provide a basic review of the 2 diseases, highlighting key neurologic concerns. We also review and update current vaccine concerns from a practitioner's perspective, including available vaccines, vaccine schedule recommendations, vaccine reactions, and risk assessment. Last, we mention the ferret and its use in cutting-edge vaccine development.
16. Jochmans, D., & Neyts, J. (2017). The path towards effective antivirals against rabies. Vaccine, 10–12. https://doi.org/10.1016/j.vaccine.2017.12.051
Abstract
Rabies virus remains an important burden of disease claiming an estimated 60,000 lives each year, mainly children, and having a huge economical and societal cost. Post-exposure prophylaxis (PEP) is highly effective, however in patients that present with neurological symptoms the case-fatality ratio is extremely high (>99%). During the last decades several attempts to identify potent and effective antivirals were made. Only a few of these demonstrated improvement in clinical signs in animal studies and none of the trials in humans showed significant efficacy. Here we explore novel opportunities to identify more potent anti-rabies molecules. In particular important progress has been made on antivirals against other Mononegavirales (paramyxoviruses, filoviruses) which should be an impetus to test and optimize these molecules towards anti-rabies virus therapies. Effective rabies antivirals for therapeutic use need to be molecules that can be dosed into the cerebrospinal fluid and that rapidly and potently block ongoing virus replication and as such stop the further spread of the virus. Antivirals for prophylactic use can also be envisaged and these should be able to prevent infection of peripheral nerve cells and should have the potential to replace the current anti-rabies immunoglobulins that are used in PEP.
17. Pfaff, F., Müller, T., Freuling, C. M., Fehlner-Gardiner, C., Nadin-Davis, S., Robardet, E., … Höper, D. (2018). In-depth genome analyses of viruses from vaccine-derived rabies cases and corresponding live-attenuated oral rabies vaccines. Vaccine. https://doi.org/10.1016/j.vaccine.2018.01.083
Abstract
Live-attenuated rabies virus strains such as those derived from the field isolate Street Alabama Dufferin (SAD) have been used extensively and very effectively as oral rabies vaccines for the control of fox rabies in both Europe and Canada. Although these vaccines are safe, some cases of vaccine-derived rabies have been detected during rabies surveillance accompanying these campaigns. In recent analysis it was shown that some commercial SAD vaccines consist of diverse viral populations, rather than clonal genotypes. For cases of vaccine-derived rabies, only consensus sequence data have been available to date and informa- tion concerning their population diversity was thus lacking. In our study, we used high-throughput sequencing to analyze 11 cases of vaccine-derived rabies, and compared their viral population diversity to the related oral rabies vaccines using pairwise Manhattan distances. This extensive deep sequencing analysis of vaccine-derived rabies cases observed during oral vaccination programs provided deeper insights into the effect of accidental in vivo replication of geneti- cally diverse vaccine strains in the central nervous system of target and non-target species under field conditions. The viral population in vaccine-derived cases appeared to be clonal in contrast to their par- ental vaccines. The change from a state of high population diversity present in the vaccine batches to a clonal genotype in the affected animal may indicate the presence of a strong bottleneck during infec- tion. In conclusion, it is very likely that these few cases are the consequence of host factors and not the result of the selection of a more virulent genotype. Furthermore, this type of vaccine-derived rabies leads to the selection of clonal genotypes and the selected variants were genetically very similar to potent SAD vaccines that have undergone a history of in vitro selection.
18. Tasioudi, K. E., Papatheodorou, D., Iliadou, P., Kostoulas, P., Gianniou, M., Chondrokouki, E., Mylonakis, M. E. (2018). Factors influencing the outcome of primary immunization against rabies in young dogs. Veterinary Microbiology, 213(November 2017), 1–4. https://doi.org/10.1016/j.vetmic.2017.11.006
Abstract
There is currently limited information on the factors influencing the outcome of rabies vaccination in dogs based on the primary immunization schedule. The objective of this study was to investigate whether selected variables (signalment, number of vaccinations, vaccine brand and multivalence, and time interval between the most recent vaccination and blood sampling) were associated with the achievement of an acceptable titer threshold (based on international standards) and with absolute antibody titers in young dogs vaccinated with commercially available vaccines. Serologic data from 662 dogs tested prior to their first annual booster for rabies were retrospectively reviewed. Neutralizing antibody titers were determined using a fluorescent antibody neutralization test. An acceptable titer threshold (≥0.5 IU/ml) was achieved in 86.5% of the dogs. Dogs that had been vaccinated twice had significantly (P < 0.001) higher antibody titers compared with dogs vaccinated once. The odds of achieving seropositivity and the median absolute antibody titer tended to decrease with increasing time between vaccination and blood sampling. Dogs vaccinated with monovalent vaccines were more likely to achieve an acceptable titer than dogs vaccinated with polyvalent vaccines. Dogs that were vaccinated after 3–6 months of age were more likely to develop higher antibody titers. These results indicate that the administration of two vaccines rather than one vaccine in the primary immunization schedule for rabies, result in a superior vaccination response and may be a more beneficial policy for ensuring pre-exposure prophylaxis and for travel certification of young dogs.
19. Seo, W., Servat, A., Cliquet, F., Akinbowale, J., Prehaud, C., Lafon, M., & Sabeta, C. (2017). Comparison of G protein sequences of South African street rabies viruses showing distinct progression of the disease in a mouse model of experimental rabies. Microbes and Infection, 19(9–10), 485–491.
https://doi.org/10.1016/j.micinf.2017.05.005
Abstract
There is currently limited information on the factors influencing the outcome of rabies vaccination in dogs based on the primary immunization schedule. The objective of this study was to investigate whether selected variables (signalment, number of vaccinations, vaccine brand and multivalence, and time interval between the most recent vaccination and blood sampling) were associated with the achievement of an acceptable titer threshold (based on international standards) and with absolute antibody titers in young dogs vaccinated with commercially available vaccines. Serologic data from 662 dogs tested prior to their first annual booster for rabies were retrospectively reviewed. Neutralizing antibody titers were determined using a fluorescent antibody neutralization test. An acceptable titer threshold (≥0.5 IU/ml) was achieved in 86.5% of the dogs. Dogs that had been vaccinated twice had significantly (P < 0.001) higher antibody titers compared with dogs vaccinated once. The odds of achieving seropositivity and the median absolute antibody titer tended to decrease with increasing time between vaccination and blood sampling. Dogs vaccinated with monovalent vaccines were more likely to achieve an acceptable titer than dogs vaccinated with polyvalent vaccines. Dogs that were vaccinated after 3–6 months of age were more likely to develop higher antibody titers. These results indicate that the administration of two vaccines rather than one vaccine in the primary immunization schedule for rabies, result in a superior vaccination response and may be a more beneficial policy for ensuring pre-exposure prophylaxis and for travel certification of young dogs.
20. Smith, T. G., Millien, M., Vos, A., Fracciterne, F. A., Crowdis, K., Chirodea, C., … Wallace, R. (2017). Evaluation of immune responses in dogs to oral rabies vaccine under field conditions. Vaccine. https://doi.org/10.1016/j.vaccine.2017.09.096
ABSTRACT
During the 20th century parenteral vaccination of dogs at central-point locations was the foundation of successful canine rabies elimination programs in numerous countries. However, countries that remain enzootic for canine rabies have lower infrastructural development compared to countries that have achieved elimination, which may make traditional vaccination methods less successful. Alternative vaccination methods for dogs must be considered, such as oral rabies vaccine (ORV). In 2016, a traditional mass dog vaccination campaign in Haiti was supplemented with ORV to improve vaccination coverage and to evaluate the use of ORV in dogs. Blisters containing live-attenuated, vaccine strain SPBNGAS-GAS were placed in intestine bait and distributed to dogs by hand. Serum was collected from 107 dogs, aged 3-12 months with no reported prior rabies vaccination, pre-vaccination and from 78/107 dogs (72.9%) 17 days post-vaccination. The rapid florescent focus inhibition test (RFFIT) was used to detect neutralizing antibodies and an ELISA to detect rabies binding antibodies. Post-vaccination, 38/41 (92.7%) dogs that received parenteral vaccine had detectable antibody (RFFIT >0.05IU/mL), compared to 16/27 (59.3%, p40% blocking, p0.05IU/mL) were detected in 10/107 reportedly vaccine-naïve dogs (9.3%). Parenteral vaccination remains the most reliable method for ensuring adequate immune response in dogs, however ORV represents a viable strategy to supplement existing parental vaccination campaigns in hard-to-reach dog populations. The hand-out model reduces the risk of unintended contact with ORV through minimizing vaccine blisters left in the community.
21. Menegas, W., Uchida, N., & Watabe-Uchida, M. (2017). A Self-Killing Rabies Virus That Leaves a Trace on the DNA. Trends in Neurosciences, 40(10), 589–591. https://doi.org/10.1016/j.tins.2017.08.005
ABSTRACT
Although modified rabies viruses have emerged as a powerful tool for tracing the inputs to genetically defined populations of neurons, the toxicity of the virus has limited its utility. A recent study employed a self-inactivating rabies (SiR) virus that enables recording or manipulation of targeted neurons for months.
22. Picot, V., Rasuli, A., Abella-Rider, A., Saadatian-Elahi, M., Aikimbayev, A., Barkia, A., … Nel, L. (2017). The Middle East and Eastern Europe rabies Expert Bureau (MEEREB) third meeting: Lyon-France (7–8 April, 2015). Journal of Infection and Public Health, 10(6), 695–701. https://doi.org/10.1016/j.jiph.2017.03.005
ABSTRACT
MEEREB is an inter-regional network of countries from North Africa, Europe, the Middle East and Central Asia that work together with the aim of improving rabies control and prevention at local, regional and global level. MEEREB members met for the third time in 2015 in France (Lyon) to review the current rabies situation within the network and to discuss the way forward the prospect of a One Health approach against rabies. Dogs were the main vector of transmission in all MEEREB countries except for Croatia and Serbia where foxes represented the primary source. The number of rabies animal cases reported in 2014 varied substantially between countries with Ukraine reporting the highest number of animal cases. Human cases still occur in North Africa and all Middle East and Eurasian countries while no cases of human rabies were reported in Croatia, Serbia and Romania, although cases of rabies were identified in both dogs and foxes in 2014. Participants concluded that MEEREB can act as a think-tank where countries can share data, information, experiences and best practices to jointly address challenges in rabies control and prevention. They called for elimination of dog-transmitted rabies through vaccine and rabies immunoglobulin stockpiles and implementation of a One Health approach to achieve rabies's eradication.
23. Haley, S. L., Tzvetkov, E. P., Lytle, A. G., Alugupalli, K. R., Plummer, J. R., & McGettigan, J. P. (2017). APRIL:TACI axis is dispensable for the immune response to rabies vaccination. Antiviral Research, 144, 130–137.
https://doi.org/10.1016/j.antiviral.2017.06.004
Abstract
There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens. Several studies have successfully employed the TNF family cytokine a proliferation-inducing ligand (APRIL) as a vaccine adjuvant. APRIL binds to the receptors TACI and B cell maturation antigen (BCMA)–expressed by B cells in various stages of maturation–with high affinity. We discovered that RABV-infected primary murine B cells upregulate APRIL ex vivo. Cytokines present at the time of antigen exposure affect the outcome of vaccination by influencing T and B cell activation and GC formation. Therefore, we hypothesized that the presence of APRIL at the time of RABV-based vaccine antigen exposure would support the generation of protective antibodies against RABV glycoprotein (G). In an effort to improve the response to RABV vaccination, we constructed and characterized a live recombinant RABV-based vaccine vector which expresses murine APRIL (rRABV-APRIL). Immunogenicity testing in mice demonstrated that expressing APRIL from the RABV genome does not impact the primary antibody response against RABV G compared to RABV alone. In order to evaluate the necessity of APRIL for the response to rabies vaccination, we compared the responses of APRIL-deficient and wild-type mice to immunization with rRABV. APRIL deficiency does not affect the primary antibody response to vaccination. Furthermore, APRIL expression by the vaccine did not improve the generation of long-lived antibody-secreting plasma cells (PCs) as serum antibody levels were equivalent in response to rRABV-APRIL and the vector eight weeks after immunization. Moreover, APRIL is dispensable for the long-lived antibody-secreting PC response to rRABV vaccination as anti-RABV G IgG levels were similar in APRIL-deficient and wild-type mice six months after vaccination. Mice lacking the APRIL receptor TACI demonstrated primary anti-RABV G antibody responses similar to wild-type mice following immunization with the vaccine vector indicating that this response is independent of TACI-mediated signals. Collectively, our findings demonstrate that APRIL and associated TACI signaling is dispensable for the immune response to RABV-based vaccination.
SCABIES
24. Hsu, R. J., Lin, C. Y., Chang, F. W., Huang, C. F., Chuang, H. C., & Liu, J. M. (2017). The association between scabies and myasthenia gravis: A nationwide population-based cohort study. Journal of Clinical Neuroscience, 45, 115–120. https://doi.org/10.1016/j.jocn.2017.08.010
Abstract
Scabies is an infectious inflammatory pruritic skin disease. Cytokine-mediated inflammatory processes contribute to the pathologic mechanism in scabies. Myasthenia gravis (MG) is also an autoimmune disease that is mediated by cytokines. The study aimed to investigate the association between scabies and myasthenia gravis. We conducted a nationwide population-based cohort study utilized data from the National Health Insurance Research Database (NHIRD) of Taiwan. Patients with scabies (n = 5429) and control subjects without scabies (n = 20,176) were enrolled. We tracked the subjects in both groups for a 7-year period to identify new onset MG. Cox regression analysis was performed to calculate the hazard ratio (HR) for MG. A total of 25,605 patients were enrolled in the study, including 5429 patients in the scabies group and 20,176 in the control group. There were 40 (0.7%) patients from the scabies group and 84 (0.4%) subjects from the control group who were newly diagnosed with MG during the 7-year follow-up period. The scabies patients had a significantly increased risk of MG, with an adjusted HR of 1.27 (95% confidence interval [CI] 1.01–1.89). As such, prompt diagnosis and treatment of scabies may decrease the risk of subsequent MG.
25. Lin, C. Y., Chang, F. W., Yang, J. J., Chang, C. H., Yeh, C. L., Lei, W. Te, … Hsu, R. J. (2017). Increased risk of bipolar disorder in patients with scabies: A nationwide population-based matched-cohort study. Psychiatry Research, 257, 14–20. https://doi.org/10.1016/j.psychres.2017.07.013
Abstract
Both scabies and bipolar disorder (BD) are common and troublesome disorders. There are several similarities in both diseases: pruritus, a higher prevalence in crowded environments, and cytokine-mediated inflammatory processes in the pathophysiology. We conducted this nationwide population-based study to investigate the possible relationship between scabies and BD. Based on the National Health Insurance Research Database (NHIRD) of Taiwan, a total of 7096 patients with scabies were identified as a study group and 28,375 matched patients as a control. We tracked the patients in both groups for a 7-year period to identify those newly diagnosed with BD. The demographic characteristics and comorbidities of the patients were analyzed, and Cox proportional hazard regressions were performed to calculate the hazard ratio (HR) of BD. Of the 35,471 patients in this study, 183 (0.5%) patients with newly diagnosed BD were identified, with 58 (0.8%) from the scabies group and 125 (0.4%) from the control group. The patients with scabies had a higher risk of subsequent BD, with a crude hazard ratio of 1.86 and an adjusted hazard ratio of 1.55 (95% confidence interval: 1.12–2.09, P < 0.05). This study shows there is an increased risk for BD among patients with scabies. Immunopathology may contribute to this association.
26. Marotta, M., Toni, F., Dallolio, L., Toni, G., & Leoni, E. (2018). Management of a family outbreak of scabies with high risk of spread to other community and hospital facilities. American Journal of Infection Control, (2017), 1–6. https://doi.org/10.1016/j.ajic.2017.12.004
ABSTRACT
BACKGROUND In developed countries, scabies is observed sporadically or as institutional outbreaks in hospitals and other health facilities. In the family context, outbreaks generally involve a limited number of cases. METHODS A local health authority in Emilia-Romagna (Northern Italy) carried out an epidemiologic investigation on a family outbreak of scabies that included an unusually high number of cases. Its possible connection with a nosocomial case in a long-term care facility (LTCF) and outbreak management are discussed. RESULTS Among the household members, 8 confirmed cases occurred (attack rate, 87.5%). Another case was reported in a patient of an LTCF where one of the family cases worked as a sociosanitary operator. In total, 244 contacts were placed under surveillance. The control strategy focused on a mass information campaign addressed to all contacts and the training of health care personnel. In addition, specific prophylaxis (permethrin 5%) was performed in 108 high-risk contacts and LTCF patients and staff. CONCLUSIONS The control measures were successful in preventing the spread of the outbreak. However, misdiagnosis and the tendency of people to hide the symptoms caused the late recognition and underestimation of the cases, contributing to delayed control measures and increasing the economic and human resources required for outbreak management.
27. Dhana, A., Yen, H., Okhovat, J.-P., Cho, E., Keum, N., & Khumalo, N. P. (2018). Ivermectin versus permethrin in the treatment of scabies: A systematic review and meta-analysis of randomized controlled trials. Journal of the American Academy of Dermatology, 78(1), 194–198. https://doi.org/10.1016/j.jaad.2017.09.006
Abstract
With the limited number of studies, there is still
insufficient evidence to make a conclusion about the effectiveness of BoNT/A in the treatment of localized chronic pruritus. Other limitations include the lack of randomized controlled trials, the small sample size in each study, the wide variety of outcome measures, and the role of placebo effect. Given these limita- tions, it is too early to recommend the regular use of BoNT/A in the treatment of chronic localized pruri- tus; however, it remains an option for the clinician in cases of recalcitrant localized pruritus. Of note, there are 3 ongoing, large-scale trials evaluating the efficacy of BoNT/A in relieving localized chronic itch caused by notalgia paresthetica, hypertrophic scars, and histamine prickeinduced itch
