Rabies post-exposure vaccination in 2 visits within a week: A 4-site intradermal regimen.

Rabies is fatal in all unvaccinated patients bitten by dogs, and so post-exposure vaccine regimens must be robust enough to ensure their survival under all conditions. Treatment tends to be excessive for most people, but there is justified anxiety about reducing vaccine dosage and shortening regimens. Recently, World Health Organisation (WHO) recommended one week primary post-exposure intradermal regimens requiring 3 clinic visits, but these are unlikely to prove economical where rabies vaccination is most needed, in deprived rural areas of Africa and Asia. A highly immunogenic regimen involving two doses of intradermal vaccine given one week apart has advantages over other regimens. Anyone exposed to a possibly rabid animal would be given intradermal (ID) injections at 4 sites using a whole vial of vaccine. Those who had not been previously vaccinated would be given 2-site ID injections using half a vial one week later. Those who might be immunosuppressed could be given an optional single ID dose on day 28. The rationale for this regimen is discussed in the context of the recently revised WHO recommendations for rabies prophylaxis.

Developments in human rabies prophylaxis.

Rabies is entirely preventable. All deaths are the result of failed prophylaxis. Rabies encephalomyelitis has never been reported in anyone who received both pre-exposure vaccination and a post-exposure booster. Awareness of the risk of contact with rabid animals is crucial. A lack of basic knowledge and the inaccessibility of expensive rabies vaccines can discourage patients bitten by suspected rabid animals from seeking prompt post-exposure prophylaxis. Similarly, people working with mammals, residents of areas where dog rabies is endemic, travellers, and others at risk often fail to take advantage of pre-exposure prophylaxis. However, since human infection by a dog rabies virus has always proved fatal in unvaccinated patients, there is understandable reluctance to accept any change in vaccine protocols. The intramuscular route of delivery is wasteful and the current, low-dose intradermal (ID) regimen is not always economical or universally trusted. A new, one-week ID regimen, using less vaccine, injected at multiple sites, and involving two clinic visits, could increase the accessibility of highly immunogenic prophylaxis and reduce the prohibitive cost. The recent 2018 World Health Organization recommendations for rabies prophylaxis are included.

La rage est une maladie parfaitement évitable. Tous les décès par rage sont le résultat d'une prophylaxie déficiente. L'encéphalomyélite rabique n'a jamais été notifiée chez des sujets ayant reçu à la fois une vaccination pré-exposition et un rappel post-exposition. Il est essentiel de prendre conscience des risques liés au contact avec des animaux enragés. L'absence de connaissances élémentaires et le coût prohibitif des vaccins contre la rage empêchent parfois les patients mordus par des animaux suspectés de rage de recourir à une prophylaxie postexposition d'urgence. De même, les personnes exposées à des mammifères de par leur profession, celles vivant dans des régions où la rage canine est endémique, les voyageurs et d'autres catégories à risque n'ont pas toujours bénéficié d'une prophylaxie pré-exposition. Étant donné que l'infection humaine par le virus de la rage canine a toujours entraîné la mort chez les patients non vaccinés, la modification des protocoles de vaccination se heurte à des réticences bien compréhensibles. L'administration du vaccin par voie intramusculaire est peu rentable, tandis que la posologie actuelle d'une faible dose administrée par voie intradermique n'est pas nécessairement moins onéreuse et ne suscite pas une confiance universelle. Un nouveau protocole de vaccination intradermique consistant à administrer moins de vaccin mais sur une semaine, en changeant les sites d'injection et en encadrant le protocole par deux examens cliniques pourrait améliorer l'accessibilité d'une prophylaxie fortement immunogène tout en réduisant son coût pour le rendre moins prohibitif. L'auteure présente les récentes (2018) recommandations de l'Organisation mondiale de la santé (OMS) en matière de prophylaxie de la rage.

La rabia es una enfermedad totalmente prevenible. Todos los casos de muerte se deben a una profilaxis defectuosa. Nunca se ha descrito encefalomielitis rábica en una persona que hubiera recibido vacunación previa a la exposición y un refuerzo tras la exposición. Un aspecto crucial es la sensibilización respecto de los riesgos ligados al contacto con animales rabiosos. La falta de conocimientos básicos y la imposibilidad de acceder a las onerosas vacunas antirrábicas pueden disuadir a pacientes mordidos por animales posiblemente rabiosos de solicitar con prontitud medidas de profilaxis tras exposición. Análogamente, tampoco las personas que trabajan con mamíferos, los residentes de zonas donde la rabia canina es endémica, los viajeros y otras personas expuestas al riesgo suelen aprovechar las posibilidades que ofrece la profilaxis previa a la exposición. No obstante, dado que hasta ahora la infección humana por un virus de la rabia canina ha resultado invariablemente letal en pacientes no vacunados, existe una comprensible reticencia a aceptar el menor cambio en los protocolos de vacunación. La administración por vía intramuscular conduce al despilfarro, y el vigente régimen de vacunación con pequeñas dosis intradérmicas no siempre resulta económico ni inspira confianza generalizada. La aplicación de un nuevo régimen de vacunación intradérmica consistente en la inyección en múltiples sitios de una menor cantidad de vacuna en apenas dos visitas al practicante en el curso de una semana puede hacer más accesible una profilaxis muy inmunógena y a la vez reducir los costos prohibitivos de la prevención. La autora expone también las recientes (2018) recomendaciones de la Organización Mundial de la Salud (OMS) en materia de profilaxis antirrábica.

Current rabies vaccines and prophylaxis schedules: preventing rabies before and after exposure.

Travellers are probably the largest group in the general population to receive rabies pre-exposure prophylaxis. The dangerous consequences of the unavailability of rabies immune globulin in many countries could be ameliorated if pre-exposure rabies vaccination were practised more widely, especially in children, living in dog rabies enzootic countries. The WHO has recommended several different regimens for post-exposure prophylaxis, while individual countries decide on protocols for local use. Intramuscular regimens are expensive and waste vaccine. Although failure to receive vaccine is usually the due to the cost, the economical potential of intradermal vaccination has still not been realised 19 years after its introduction. The currently recommended 2-site intradermal post-exposure regimen is not economical for use in rural areas where 80% of Indian rabies deaths occur. Most countries using it demand higher potency vaccine, indicating that they do not have complete confidence in the method. This intradermal regimen has only been used where immunoglobulin is likely to be available for severely bitten patients. Increased intradermal doses are sometimes used for selected patients. Provision of economical rabies prophylaxis can be improved. Decisions to change recommendations should take account of the immunological, financial, practical and logistical aspects of dog bite treatment in remote areas.

Intradermal rabies vaccination: the evolution and future of pre- and post-exposure prophylaxis.

Inactivated rabies vaccines have been used to pioneer the immunological and economical advantages of intradermal (ID) administration over 35 years. Vaccine shortages or its prohibitive cost stimulated studies of various doses, frequency and sites of injection. An economical regimen for pre-exposure prophylaxis requires one-tenth of an intramuscular dose, but the early popularity of the method has been stifled by pharmaceutical regulations. There has also been reluctance to use multiple-site post-exposure ID regimens, except in a very few Asian counties. A new four-site ID regimen could overcome many of the problems encountered to date. The time is ripe to make dramatic progress towards efficient use of the current excellent vaccines globally, wherever there is a shortage of vaccine or funds.

Rabies and other lyssavirus diseases.

The full scale of the global burden of human rabies is unknown, owing to inadequate surveillance of this fatal disease. However, the terror of hydrophobia, a cardinal symptom of rabies encephalitis, is suffered by tens of thousands of people each year. The recent discovery of enzootic European bat lyssavirus infection in the UK is indicative of our expanding awareness of the Lyssavirus genus. The main mammalian vector species vary geographically, so the health problems created by the lyssaviruses and their management differ throughout the world. The methods by which these neurotropic viruses hijack neurophysiological mechanisms while evading immune surveillance is beginning to be unravelled by, for example, studies of molecular motor transport systems. Meanwhile, enormous challenges remain in the control of animal rabies and the provision of accessible, appropriate human prophylaxis worldwide.

Neurological manifestations of dengue infection.

BACKGROUND: Severe forms of dengue, the most important arboviral infection of man, are associated with haemorrhagic disease and a generalised vascular leak syndrome. The importance of dengue as a cause of neurological disease is uncertain. METHODS: During 1995, all patients with suspected CNS infections admitted to a referral hospital in southern Vietnam were investigated by culture, PCR, and antibody measurement in serum and CSF for dengue and other viruses. FINDINGS: Of 378 patients, 16 (4.2%) were infected with dengue viruses, compared with four (1.4%) of 286 hospital controls (odds ratio [95% CI] 3.1 [1.7-5.8]). Five additional dengue positive patients with CNS abnormalities were studied subsequently. No other cause of CNS infection was identified. Seven infections were primary dengue, 13 secondary, and one was not classified. Ten patients had dengue viruses isolated or detected by PCR, and three had dengue antibody in the CSF. 12 of the 21 had no characteristic features of dengue on admission. The most frequent neurological manifestations were reduced consciousness and convulsions. Nine patients had encephalitis. No patient died, but six had neurological sequelae at discharge. Phylogenetic analysis of the four DEN-2 strains isolated mapped them with a DEN-2 strain isolated from a patient with dengue haemorrhagic fever, and with other strains previously isolated in southern Vietnam. INTERPRETATION: In dengue endemic areas patients with encephalitis and encephalopathy should be investigated for this infection, whether or not they have other features of the disease.

Human rabies: a continuing challenge in the tropical world.

More than 99% of all human rabies deaths in the world occur in tropical developing countries. In India alone, 30,000 to 50,000 people may die of rabies each year. The Lyssaviruses (Family Rhabdoviridae) include rabies and rabies-related viruses, 3 of which have caused human disease. Rabies is a zoonosis, principally affecting domestic and stray dogs in most parts of Africa, Asia and Latin America. In North America, southern Africa, parts of the Caribbean and Europe, the principal mammalian reservoir species are wild carnivores. The pathogenesis, clinical features and differential diagnosis of rabies are discussed. The planning of rabies control strategies requires background information on the distribution and incidence of rabies in animals and the species involved. In some parts of the world, such as Latin American cities, most domestic dogs, even apparent strays, have an owner and can be immunized with conventional canine vaccines during well publicized campaigns. However, in areas such as India, where there may be a high proportion of stray domestic dogs without owners, and in those areas where wild mammals are the principal reservoir species, immunization may be possible using live attenuated or recombinant oral vaccines distributed in baits. In the poor tropical developing countries, unsatisfactory nervous tissue vaccines are still widely used. However, economical multisite intradermal regimens using tissue culture vaccines have proved effective and have begun to replace nervous tissue vaccines in some countries.

Intradermal rabies immunization for pre- and post-exposure prophylaxis.

Human diploid cell rabies vaccine and similar tissue culture-produced vaccines are too expensive for widespread use in India, but alternative regimes can reduce the cost of post-exposure treatment by 60%. Multiple-site intradermal injections of tissue culture vaccine have proved effective, economical and safe. As these vaccines are becoming more freely available, the intradermal method can now be used to accelerate the replacement of nervous tissue vaccines.

Failure of interferon alfa and tribavirin in rabies encephalitis.

OBJECTIVE: To test the effect of interferon alfa and tribavirin (ribavirin) in patients with rabies encephalitis. DESIGN: An open trial of chemotherapy and intensive care in patients with early rabies. SETTING: The intensive care unit of a Bangkok hospital. PATIENTS: Four conscious men with clinical rabies encephalitis. INTERVENTIONS: Rapid virological diagnosis of rabies. Treatment with intravenous and intraventricular injections of high doses of lymphoblastoid interferon alfa in three patients and tribavirin in one patient. Intensive care was given throughout. MAIN OUTCOME MEASURES: Rabies infection confirmed by antigen detection and virus isolation. Rabies neutralising antibody and specific IgM sought in serum and cerebrospinal fluid. Interferon concentrations monitored before and during treatment in three patients. RESULTS: Interferon alfa treatment produced high concentrations in serum and cerebrospinal fluid. All four patients died after 5 1/2 to 12 1/2 days of treatment with no evidence of virostatic or clinically beneficial effects from either treatment. CONCLUSION: Interferon alfa treatment is not effective in rabies encephalitis. The use of tribavirin warrants further study, possibly combined with new therapeutic methods.

Human rabies and its prevention: an overview.

Human rabies is underreported, but it clearly is still a frequent medical problem that is virtually confined to tropical countries. Rabies encephalitis remains essentially incurable, and most patients die at home, their terrible symptoms unpalliated by sedatives or analgesics. Recent attempts to cure rabies in well-equipped intensive care units have failed, a situation reemphasizing the importance of preventive measures. The great advances that have been made in understanding the rabies virus and the associated improvements in rabies vaccines have had little or no impact in the tropical endemic zone. Most patients who have been exposed to rabies are still given nervous tissue vaccines for postexposure prophylaxis. An urgent priority is the development of a regimen using tissue culture vaccine that is sufficiently economical to replace nervous tissue vaccine. This has been achieved in China with primary hamster kidney cell vaccine.

Rapid diagnosis of rabies and post-vaccinal encephalitides.

In an attempt to establish the diagnoses of rabies post-vaccinal encephalitis (PVE) and early rabies encephalitis, paired serum and CSF levels of rabies neutralizing antibody (Rab) and rabies specific-IgM (RIgM) were compared in 12 PVE, 10 rabies and five control patients with similar presenting clinical features. Rapid methods of rabies antigen detection were evaluated in 17 patients. All 12 PVE patients had Rab in their serum and in eight it was also present in the CSF. These same eight had RIgM in the serum, and in seven also in the CSF. The CSF antibodies may have originated in the plasma since six patients had a high albumin quotient indicating leakage across the blood-brain barrier. Among the rabies patients, only the two vaccinated ones had serum Rab; this was also detected in the CSF of one and RIgM was in the CSF of the other. A raised IgG Index, indicating intrathecal synthesis of IgG was seen in five of 12 PVE patients. This did not correlate with the presence of CSF rabies antibody, suggesting production of antibody to other vaccine antigens of neural origin. The diagnosis of rabies encephalitis in life was made by antigen detection in a skin biopsy. No false positive results occurred and the method was as efficient as immunofluorescence of a post-mortem brain biopsy.