- Email: [email protected]
Rabies and other lyssavirus diseases
CORRESPONDENCE
COMMENTARY
CORRESPONDENCE e-mail submissions to [email protected]
Rabies and other lyssavirus diseases Sir—We wish to compliment M J Warrell and D A Warrell on their scholarly Seminar (Mar 20, p 959).1 It is an excellent overview of a neglected topic. Two comments might be of interest. First, we have found that rabies virus RNA can be identified in saliva, cerebrospinal fluid, and urine, but only intermittently and not in blood.2,3 If saliva, cerebrospinal fluid, and urine were tested simultaneously (and repeatedly if the first sample was negative) by nucleic acid sequencebased amplification, we were able to make the diagnosis in 21 of 23 patients. Second, a recent post-exposure treatment failure in a 7-year-old Thai girl, who had prompt wound care of head and face bites followed by application of the eight-site regimen without rabies immunoglobulin (RIG), should serve as a warning that RIG is still an essential biological. The attending physicians had no RIG and, on reading in a local rabies information sheet that RIG might not be necessary when the eight-site schedule is used, did not refer the child to a nearby higher level of care.4 Our study confirmed that the eight-site schedule results in higher antibody titres by day 14 than the five-full-dose intramuscular or two-site intradermal regimens.5 However, it did not show any significantly earlier antibody responses on days 5 and 7—the time when virus can enter peripheral nerves and thus be in an immune-protected environment. We wish that the rabies Seminar had clarified this issue, rather than creating another source of confusion about optimum post-exposure rabies treatment. Prevention of human rabies depends on provision of affordable post-exposure treatment, administering human or purified equine RIG into and around bite wounds, and, above all, control of the disease in dogs. *Henry Wilde, Thiravat Hemachudha, Terapong Tantawichien, Pakamatz Khawplod Department of Medicine, Chulalongkorn University and Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok 10330, Thailand (e-mail: [email protected])
1906
1
2
3
4
5
Warrell MJ, Warrell DA. Rabies and other lyssavirus diseases. Lancet 2004; 363: 959–69. Sitprija V, Sriaroon C, Lumlertdaecha B, et al. Does contact with urine and blood from a rabid dog represent rabies risk? Clin Infect Dis 2003; 37: 1399–400. Wacharapluesadee S, Hemachudha T. Urine for rabies RNA detection in the diagnosis of rabies in humans. Clin Infect Dis 2002; 34: 874–75. Sriaroon C, Daviratanasilpa S, Sansomranjai P, et al. Rabies in a Thai child treated with the eight-site post-exposure regimen without rabies immune globulin. Vaccine 2003; 21: 3525–26. Khawplod P, Wilde H, Tepsumethanon S, et al. Prospective immunogenicity study of multiple intradermal injections of rabies vaccine in an effort to obtain an early immune response without use of immunoglobulin. Clin Infect Dis 2002; 35: 1562–65.
Sir—An important milestone in the understanding of rabies was the demonstration of Negri bodies by Adelchi Negri in 1903.1 These structures were thought to represent a stage in the life-cycle of the protozoan parasite. Surprisingly, Negri bodies do not find a place in the excellent Seminar on rabies and other lyssavirus diseases by M J Warrell and D A Warrell.2 Have these bodies become fossilised and lost their relevance in the present day? Negri bodies are well defined, oval or elongated eosinophilic cytoplasmic inclusions in neurons. Each eosinophilic mass measures 10 nm and is made up of a fine fibrillar matrix and rabies virus particles. These bodies are distributed throughout the brain, particularly in Ammon’s horn, the cerebral cortex, brainstem, hypothalamus, Purkinje cells of the cerebellum, and dorsal spinal ganglia. Negri bodies are seen in about 80% of cases of rabies, but their absence does not exclude such a diagnosis.3,4 In a series of 49 fatal cases of rabies reported from the Armed Forces Institute of Pathology, Washington DC, USA. Negri bodies were found in 35. Negri bodies are larger and more abundant in patients who survive for more than 4–5 days and can be difficult to find in patients who succumb during the first 48 h.4 In the first half of the 20th century, examination of the brain for Negri bodies was the main laboratory test
for rabies until immunofluorescent methods were introduced in the 1950s and 1960s. Negri bodies have therefore lost some of their diagnostic importance as a result of this rapid, more specific, and less labour-intensive technique.5 All the same, demonstration of Negri bodies still remains important in the diagnosis of rabies in developing countries, where the disease is endemic and where immunofluorescence facilities might not be available. In our institution we diagnose rabies by a combination of the two techniques. *Ajit Kashyap, Kuldip Anand, Surekha Kashyap Departments of *Medicine (AK, KA) and Hospital Administration (SK), Armed Forces Medical College, Pune 411 040, India (e-mail: [email protected]) 1
2
3
4
5
Negri A. Beitragzumstudium der Aetiologie der Tollwuth. Zeitschrift fur Hygiene and Infektionskrankheiten 1903; 43: 507–28. Warrell MJ, Warrell DA. Rabies and other lyssavirus diseases. Lancet 2004; 363: 959–69. Corey L. Rabies virus and other rhabdoviruses. In: Braunwald E, Fauci AS, Kasper DL, eds. Harrison’s principles of internal medicine, 15th edn, vol 1. New York: McGraw-Hill, 2001: 1149–52. Basgoz N, Fosch M. Case records of Massachusetts general hospital. Case 21-1998. N Engl J Med 1998; 339: 105–12. Tardo N, Charlton K, Wandeler A. Rhabdoviruses: rabies. In: Mahy BWJ, Collier L, eds. Topley and Wilson’s microbiology and microbial infections, 9th edn, vol I. New York: Oxford University Press, 2003: 665–92.
Sir—In their Seminar on rabies,1 M J Warrell and D A Warrell do not consider the possibility of mass human rabies vaccination as a method of disease control. Human rabies vaccines in use today are based on inactivated live virus, and are thought to work by eliciting neutralising antibodies to envelope glycoprotein. These vaccines are expensive to prepare and carry the theoretical risk of transmission of live virus if inadequately inactivated. Precisely this problem led Aventis Pasteur to withdraw several vaccine lots in April, 2004, with administration of post-exposure prophylaxis to affected individuals. Recombinant vaccinia virus expressing rabies envelope glycoprotein has been successfully used to control animal
THE LANCET • Vol 363 • June 5, 2004 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
COMMENTARY
CORRESPONDENCE e-mail submissions to [email protected]
Rabies and other lyssavirus diseases Sir—We wish to compliment M J Warrell and D A Warrell on their scholarly Seminar (Mar 20, p 959).1 It is an excellent overview of a neglected topic. Two comments might be of interest. First, we have found that rabies virus RNA can be identified in saliva, cerebrospinal fluid, and urine, but only intermittently and not in blood.2,3 If saliva, cerebrospinal fluid, and urine were tested simultaneously (and repeatedly if the first sample was negative) by nucleic acid sequencebased amplification, we were able to make the diagnosis in 21 of 23 patients. Second, a recent post-exposure treatment failure in a 7-year-old Thai girl, who had prompt wound care of head and face bites followed by application of the eight-site regimen without rabies immunoglobulin (RIG), should serve as a warning that RIG is still an essential biological. The attending physicians had no RIG and, on reading in a local rabies information sheet that RIG might not be necessary when the eight-site schedule is used, did not refer the child to a nearby higher level of care.4 Our study confirmed that the eight-site schedule results in higher antibody titres by day 14 than the five-full-dose intramuscular or two-site intradermal regimens.5 However, it did not show any significantly earlier antibody responses on days 5 and 7—the time when virus can enter peripheral nerves and thus be in an immune-protected environment. We wish that the rabies Seminar had clarified this issue, rather than creating another source of confusion about optimum post-exposure rabies treatment. Prevention of human rabies depends on provision of affordable post-exposure treatment, administering human or purified equine RIG into and around bite wounds, and, above all, control of the disease in dogs. *Henry Wilde, Thiravat Hemachudha, Terapong Tantawichien, Pakamatz Khawplod Department of Medicine, Chulalongkorn University and Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok 10330, Thailand (e-mail: [email protected])
1906
1
2
3
4
5
Warrell MJ, Warrell DA. Rabies and other lyssavirus diseases. Lancet 2004; 363: 959–69. Sitprija V, Sriaroon C, Lumlertdaecha B, et al. Does contact with urine and blood from a rabid dog represent rabies risk? Clin Infect Dis 2003; 37: 1399–400. Wacharapluesadee S, Hemachudha T. Urine for rabies RNA detection in the diagnosis of rabies in humans. Clin Infect Dis 2002; 34: 874–75. Sriaroon C, Daviratanasilpa S, Sansomranjai P, et al. Rabies in a Thai child treated with the eight-site post-exposure regimen without rabies immune globulin. Vaccine 2003; 21: 3525–26. Khawplod P, Wilde H, Tepsumethanon S, et al. Prospective immunogenicity study of multiple intradermal injections of rabies vaccine in an effort to obtain an early immune response without use of immunoglobulin. Clin Infect Dis 2002; 35: 1562–65.
Sir—An important milestone in the understanding of rabies was the demonstration of Negri bodies by Adelchi Negri in 1903.1 These structures were thought to represent a stage in the life-cycle of the protozoan parasite. Surprisingly, Negri bodies do not find a place in the excellent Seminar on rabies and other lyssavirus diseases by M J Warrell and D A Warrell.2 Have these bodies become fossilised and lost their relevance in the present day? Negri bodies are well defined, oval or elongated eosinophilic cytoplasmic inclusions in neurons. Each eosinophilic mass measures 10 nm and is made up of a fine fibrillar matrix and rabies virus particles. These bodies are distributed throughout the brain, particularly in Ammon’s horn, the cerebral cortex, brainstem, hypothalamus, Purkinje cells of the cerebellum, and dorsal spinal ganglia. Negri bodies are seen in about 80% of cases of rabies, but their absence does not exclude such a diagnosis.3,4 In a series of 49 fatal cases of rabies reported from the Armed Forces Institute of Pathology, Washington DC, USA. Negri bodies were found in 35. Negri bodies are larger and more abundant in patients who survive for more than 4–5 days and can be difficult to find in patients who succumb during the first 48 h.4 In the first half of the 20th century, examination of the brain for Negri bodies was the main laboratory test
for rabies until immunofluorescent methods were introduced in the 1950s and 1960s. Negri bodies have therefore lost some of their diagnostic importance as a result of this rapid, more specific, and less labour-intensive technique.5 All the same, demonstration of Negri bodies still remains important in the diagnosis of rabies in developing countries, where the disease is endemic and where immunofluorescence facilities might not be available. In our institution we diagnose rabies by a combination of the two techniques. *Ajit Kashyap, Kuldip Anand, Surekha Kashyap Departments of *Medicine (AK, KA) and Hospital Administration (SK), Armed Forces Medical College, Pune 411 040, India (e-mail: [email protected]) 1
2
3
4
5
Negri A. Beitragzumstudium der Aetiologie der Tollwuth. Zeitschrift fur Hygiene and Infektionskrankheiten 1903; 43: 507–28. Warrell MJ, Warrell DA. Rabies and other lyssavirus diseases. Lancet 2004; 363: 959–69. Corey L. Rabies virus and other rhabdoviruses. In: Braunwald E, Fauci AS, Kasper DL, eds. Harrison’s principles of internal medicine, 15th edn, vol 1. New York: McGraw-Hill, 2001: 1149–52. Basgoz N, Fosch M. Case records of Massachusetts general hospital. Case 21-1998. N Engl J Med 1998; 339: 105–12. Tardo N, Charlton K, Wandeler A. Rhabdoviruses: rabies. In: Mahy BWJ, Collier L, eds. Topley and Wilson’s microbiology and microbial infections, 9th edn, vol I. New York: Oxford University Press, 2003: 665–92.
Sir—In their Seminar on rabies,1 M J Warrell and D A Warrell do not consider the possibility of mass human rabies vaccination as a method of disease control. Human rabies vaccines in use today are based on inactivated live virus, and are thought to work by eliciting neutralising antibodies to envelope glycoprotein. These vaccines are expensive to prepare and carry the theoretical risk of transmission of live virus if inadequately inactivated. Precisely this problem led Aventis Pasteur to withdraw several vaccine lots in April, 2004, with administration of post-exposure prophylaxis to affected individuals. Recombinant vaccinia virus expressing rabies envelope glycoprotein has been successfully used to control animal
THE LANCET • Vol 363 • June 5, 2004 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.