The Rhabdoviridae are a large family of RNA viruses, two genera of which infect animals: the genus Lyssavirus contains rabies and rabies-related viruses that cause at least 55,000 deaths annually in Asia and Africa. The risks and problems posed by rabies and other lyssaviruses vary across the world. Viruses can penetrate broken skin and intact mucosae. Humans are usually infected when virus-laden saliva is inoculated through the skin by the bite of a rabid animal, usually a dog. Although the greatest threat to man is the persistent cycle of infection in stray dogs, several other terrestrial mammal species are reservoirs of infection. In the Americas, bat viruses and also classic type 1 rabies and insectivorous bats have become the principal vectors of infection to humans in the United States of America. Elsewhere in the world, there is increasing evidence of widespread rabies-related lyssavirus infection of bats.

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.

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 humaine acquise des chiens et d'autres mammifères terrestres reste mortelle à 100%. Beaucoup d'autres patients atteints de la rage et traités avec des soins intensifs experts décèdent dans la phase aiguë ou se retrouvent avec de sévères troubles neurologiques. Avec un tel tableau et aucun traitement antiviral spécifique, comment les cliniciens devraient‐ils prendre en charge les patients atteints de cette maladie épouvantable, en particulier dans les pays pauvres où la rage canine est endémique?

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.

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.

Treatment with Semple or suckling mouse brain rabies vaccines persists in many countries of Asia, Africa and South America. Its replacement depends on the immediate accessibility of effective affordable alternative treatment with tissue culture vaccines (TCVs). The use of the expensive European TCVs has been possible in Asia by means of economical intradermal (ID) post-exposure vaccine regimens. Implementation of this effective economical treatment has been delayed by the complexity and inconvenience of the regimens, and the reluctance to change prophylaxis against a fatal disease. Up to now, the ID regimens have been used only where passive immunisation with rabies immune globulin (RIG) is usually available. Rabies deaths despite optimal vaccine treatment have been attributed to lack of RIG. The ID regimens might soon be promoted in areas where RIG is not even available for severe exposure. It is therefore vital that economical vaccine regimens should be used which induce protective immunity rapidly. Improvements in rabies pet in developing countries could be made by: (i). publicising the urgency and efficacy of wound cleaning; (ii). facilitating the replacement of nervous tissue vaccines by economical ID treatment with TCVs; (iii). using an ID regimen with a large dose of vaccine on the first day of treatment especially when no RIG is available; and (iv). promoting pre-exposure prophylaxis to eliminate the need for RIG and provide better rabies prophylaxis.

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 haemorhagic 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.

Sir, In their editorial ( Q J Med 1999; 92 :683–7) Bellamy and Salmon mention the veterinary and zoonotic pathogens which may be imported from mainland Europe and rabies‐free (‘designated’) areas, when the …

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.

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.

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.

A fatal case of encephalitis due to Semple (phenolized sheep-brain) anti-rabies vaccine prompted a search for neurological complications among 722 recipients of 2 vaccine batches administered in Bangkok, Thailand in June and July 1984. A review of all patients admitted with neurological symptoms from June through August 1984 to the 5 major teaching hospitals in Bangkok found 6 cases (0.83%), including the index case, who had received the vaccine. Rabies infection was ruled out in all 6 cases. 4 patients had meningitis, and 2 had meningo-encephalitis. Only the index case was fatal; the other patients recovered without neurological sequelae. The rate of neurological complications after receiving Semple vaccine was therefore a minimum of 8.31 cases per 1000 persons vaccinated (1:120). This complication rate was about 25 times higher than the overall complication rate of 0.33 per 1000 (1:3018) determined from 14 previous reports. The fatality rate was 1.39 per 1000 (1:722), about 15 times higher than the rate of 0.09 per 1000 (1:10805) calculated from the previous studies. It is urgent to find economically feasible alternatives to Semple vaccine.

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.