safety of equine rabies immune globulin

1
1275 INTERVAL FROM CUSUM CHANGE TO DATE OF CONFIRMED RELAPSE IN 18 CHILDREN WITH ALL *No difference in cases E and K—N. tNo cusum change in cases O-R CCR = continuous complete remission; PB = peripheral blood. detected in only 5 of the 8 patients who relapsed after the end of treatment. Cusum analysis of Hb and WBC and platelet counts extracts information from the blood-count not seen by scrutinising or plotting individual results. The method amplifies the small changes in blood-count data that occur before obvious cytopenias develop and enable early trends in blood-count to be detected against an often abnormal background. Changes in the cusum for Hb and WBC and platelet counts will also indicate changes in the peripheral blood-count which may have occurred for reasons other than relapse. There were 9 episodes where a cusum change was immediately followed by bone-marrow aspiration. These aspirates confirmed that treatment had been responsible for the change rather than relapse. Cusum analysis cannot discriminate between treatment effect and relapse. It can, however, allow more sensitive monitoring of Hb, WBC, and platelets, and provide an objective indication for bone-marrow aspiration. Haematologists might find a similar approach useful in monitoring blood-data. Department of Haematology, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN G. J. MORGAN S. THOMAS I. CAVILL D. P. BENTLEY 1. Haworth C, Hepplestone AD, Morns-Jones PH, Campbell RHA, Evans DIK, Palmer MK. Routine bone marrow examination in the management of ALL of childhood. J Clin Pathol 1981; 3: 483-85. 2. Watson DK, Robinson AE, Bailey CC. A reappraisal of routine marrow examination in the therapy of ALL. Arch Dis Child 1981; 56: 392-404. 3 Komp DM, Fischer DB, Sabio H, McIntosh S. Frequency of bone marrow aspirates to monitor ALL in childhood. J Pediatr 1983; 192: 395-97 4 British Standard Institute BS 5703, 1980 part 1 and 2. 5 Chaput de Samtonge DM, Vere DW. Why don’t doctors use cusums. Lancet 1974, i: 120-21. 6 Freedman L. Cusums. Lancet 1974, i 741-42. SAFETY OF EQUINE RABIES IMMUNE GLOBULIN SIR,-Human rabies immune globulin (HRIG) is the product of choice for early passive protection of patients exposed to rabies.1-3 However, few patients in countries where rabies is still a major public health problem can afford it. In Thailand, for example, over 100 000 individuals are given post-exposure rabies treatment every year, and 250-300 deaths are reported. HRIG costs$285, or the equivalent of at least 100 days wages for an average Thai labourer. The same man would have to work for only 9 days to pay for purified equine rabies immune globulin (ERIG). Most patients treated for rabies exposure in Thailand still receive vaccine alone, and if immune globulin is administered it is almost always of equine origin. Our institution treats 1200-1400 such patients every month: more than 95 % now receive a tissue culture vaccine ’Verorab- TRC’) and 30% or so are also given immune globulin; (ERIG in 95% and HRIG in 5% of cases). Our staff have long had the impression that the rate of local and systemic immediate or delayed serum sickness reactions is low. None could remember an anaphylactic reaction, and they could recall only 1 patient in the past year who required a short course of steroids for serum sickness. This is in sharp contrast to warnings in textbooksm3 of a 20-50% frequency of serum sickness when ERIG is used. We decided to study 500 successive Thai patients who required rabies immune globulin. 278 were male and 222 female; ages ranged from 1 to 84 years. All patients were followed up for a month or more after the injection of Pasteur Vaccins ERIG (8 were given the Swiss Serum and Vaccine Institute’s product instead). All patients were skin tested by the intradermal administration of ERIG in a 1 in 10 dilution, raising a bleb 3 mm in diameter. Skin tests were read independently by two staff members. Any wheal or flare greater than 5 mm was considered positive. There were no untoward reactions to the skin test. All 59 patients with a positive skin test were offered HRIG, but only 15 could afford it, the other 44 being given ERIG under close observation and after oral administration of antihistamines. 22 of these 44 had a wheal and/or flare greater than 10 mm. None of them had any immediate local or systemic symptoms or delayed serum-sickness-like reactions. Only 4 of the 485 patients given ERIG had any delayed type hypersensitivity reactions, and none of the 4 had had a positive skin test. In these 4 women aged 20, 25, 37, and 52 symptoms appeared 6, 7, 10, and 12 days after ERIG was given. The symptoms were fever (2), discomfort at the injection site (2), arthralgia (1), urticaria (1), and a generalised erythematous rash (3). The only treatment was an oral antihistamine and all 4 patients recovered fully within a week. We conclude that ERIG (Pasteur Vaccins) is a safe product and has an adverse reaction rate of less than 1 % in Thai patients given 40 IU/kg as an intramuscular and bite-site injection. Our previous experience with Swiss ERIG leads us to believe that it is equally safe. Science Division, Thai Red Cross Society, Queen Saovabha Memorial Institute, Bangkok 10500, Thailand HENRY WILDE PRANEE CHOMCHEY SOMPOB PRAKONGSRI POR PUNYARATABANDHU 1. Kaplan C, Tunes GS, Warrell DA. Rabies. the facts. Oxford Oxford University Press, 1986. 64. 2 Corey L. Rabies. In: Harrison’s principles of internal medicine. New York: McGraw-Hill, 1987;714. 3. Baer GM. In: Kurstake’s control of virus diseases. New York: Marcel Dekker, 1984: 86 DNA PROBES WHICH UNAMBIGUOUSLY DISTINGUISH TAENIA SOLIUM FROM T SAGINATA SIR,--Clinicians want a diagnostic test that distinguishes infestations with the "pig" tapeworm Taenia solium from those with the "beef ’ tapeworm T saginata.1 Both species are highly host-specific in that the adult worm occurs only in the small intestine of man. However, in contrast to T saginata, eggs of T solium can also develop in man to the cysticercus or larval stage. This can lead to serious and often fatal disease (cysticercosis) due to the frequent involvement of the central nervous system.2 In chronic cases (neurocysticercosis), larvae lodge in the brain, often causing epilepsy and death.2 The difficulties in distinguishing members of the taeniid group of cestodes are well recognised.3 Morphological procedures are imperfect for human taeniids because the scolex is rarely voided and the diagnosis has to rely on one or a few expelled proglottids which may be poorly preserved. When suspected cases have been treated (eg, with praziquantel) morphological characters such as the structure of the ovary and the number of uterine branches are likely to be unreliable. Inter-species differences can be detected biochemically (eg, by electrophoresis of total proteins° and enzyme electrophoresis5,6). The electrophoretic patterns are difficult to interpret, and the parasite material has to be immediately processed

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1275

INTERVAL FROM CUSUM CHANGE TO DATE OF CONFIRMED

RELAPSE IN 18 CHILDREN WITH ALL

*No difference in cases E and K—N.tNo cusum change in cases O-RCCR = continuous complete remission; PB = peripheral blood.

detected in only 5 of the 8 patients who relapsed after the end oftreatment.

Cusum analysis of Hb and WBC and platelet counts extractsinformation from the blood-count not seen by scrutinising orplotting individual results. The method amplifies the small changesin blood-count data that occur before obvious cytopenias developand enable early trends in blood-count to be detected against anoften abnormal background. Changes in the cusum for Hb andWBC and platelet counts will also indicate changes in the peripheralblood-count which may have occurred for reasons other than

relapse. There were 9 episodes where a cusum change wasimmediately followed by bone-marrow aspiration. These aspiratesconfirmed that treatment had been responsible for the change ratherthan relapse. Cusum analysis cannot discriminate betweentreatment effect and relapse. It can, however, allow more sensitivemonitoring of Hb, WBC, and platelets, and provide an objectiveindication for bone-marrow aspiration. Haematologists might find asimilar approach useful in monitoring blood-data.

Department of Haematology,University of Wales College of Medicine,Heath Park, Cardiff CF4 4XN

G. J. MORGANS. THOMASI. CAVILL

D. P. BENTLEY

1. Haworth C, Hepplestone AD, Morns-Jones PH, Campbell RHA, Evans DIK,Palmer MK. Routine bone marrow examination in the management of ALL ofchildhood. J Clin Pathol 1981; 3: 483-85.

2. Watson DK, Robinson AE, Bailey CC. A reappraisal of routine marrow examinationin the therapy of ALL. Arch Dis Child 1981; 56: 392-404.

3 Komp DM, Fischer DB, Sabio H, McIntosh S. Frequency of bone marrow aspiratesto monitor ALL in childhood. J Pediatr 1983; 192: 395-97

4 British Standard Institute BS 5703, 1980 part 1 and 2.5 Chaput de Samtonge DM, Vere DW. Why don’t doctors use cusums. Lancet 1974, i:

120-21.6 Freedman L. Cusums. Lancet 1974, i 741-42.

SAFETY OF EQUINE RABIES IMMUNE GLOBULIN

SIR,-Human rabies immune globulin (HRIG) is the product ofchoice for early passive protection of patients exposed to rabies.1-3However, few patients in countries where rabies is still a majorpublic health problem can afford it. In Thailand, for example, over100 000 individuals are given post-exposure rabies treatment everyyear, and 250-300 deaths are reported. HRIG costs$285, or theequivalent of at least 100 days wages for an average Thai labourer.The same man would have to work for only 9 days to pay forpurified equine rabies immune globulin (ERIG). Most patientstreated for rabies exposure in Thailand still receive vaccine alone,

and if immune globulin is administered it is almost always of equineorigin. Our institution treats 1200-1400 such patients every month:more than 95 % now receive a tissue culture vaccine ’Verorab-

TRC’) and 30% or so are also given immune globulin; (ERIG in95% and HRIG in 5% of cases).Our staff have long had the impression that the rate of local and

systemic immediate or delayed serum sickness reactions is low.None could remember an anaphylactic reaction, and they couldrecall only 1 patient in the past year who required a short course ofsteroids for serum sickness. This is in sharp contrast to warnings intextbooksm3 of a 20-50% frequency of serum sickness when ERIGis used. We decided to study 500 successive Thai patients whorequired rabies immune globulin. 278 were male and 222 female;ages ranged from 1 to 84 years. All patients were followed up for amonth or more after the injection of Pasteur Vaccins ERIG (8 weregiven the Swiss Serum and Vaccine Institute’s product instead).

All patients were skin tested by the intradermal administration ofERIG in a 1 in 10 dilution, raising a bleb 3 mm in diameter. Skintests were read independently by two staff members. Any wheal orflare greater than 5 mm was considered positive. There were nountoward reactions to the skin test. All 59 patients with a positiveskin test were offered HRIG, but only 15 could afford it, the other44 being given ERIG under close observation and after oraladministration of antihistamines. 22 of these 44 had a wheal and/orflare greater than 10 mm. None of them had any immediate local or

systemic symptoms or delayed serum-sickness-like reactions.Only 4 of the 485 patients given ERIG had any delayed type

hypersensitivity reactions, and none of the 4 had had a positive skintest. In these 4 women aged 20, 25, 37, and 52 symptoms appeared6, 7, 10, and 12 days after ERIG was given. The symptoms werefever (2), discomfort at the injection site (2), arthralgia (1), urticaria(1), and a generalised erythematous rash (3). The only treatmentwas an oral antihistamine and all 4 patients recovered fully within aweek.We conclude that ERIG (Pasteur Vaccins) is a safe product and

has an adverse reaction rate of less than 1 % in Thai patients given40 IU/kg as an intramuscular and bite-site injection. Our previousexperience with Swiss ERIG leads us to believe that it is equallysafe.

Science Division,Thai Red Cross Society,Queen Saovabha Memorial Institute,Bangkok 10500, Thailand

HENRY WILDEPRANEE CHOMCHEYSOMPOB PRAKONGSRIPOR PUNYARATABANDHU

1. Kaplan C, Tunes GS, Warrell DA. Rabies. the facts. Oxford Oxford UniversityPress, 1986. 64.

2 Corey L. Rabies. In: Harrison’s principles of internal medicine. New York:

McGraw-Hill, 1987;714.3. Baer GM. In: Kurstake’s control of virus diseases. New York: Marcel Dekker, 1984:

86

DNA PROBES WHICH UNAMBIGUOUSLYDISTINGUISH TAENIA SOLIUM FROM T SAGINATA

SIR,--Clinicians want a diagnostic test that distinguishesinfestations with the "pig" tapeworm Taenia solium from those withthe "beef ’ tapeworm T saginata.1 Both species are highlyhost-specific in that the adult worm occurs only in the smallintestine of man. However, in contrast to T saginata, eggs ofT solium can also develop in man to the cysticercus or larval stage.This can lead to serious and often fatal disease (cysticercosis) due tothe frequent involvement of the central nervous system.2 In chroniccases (neurocysticercosis), larvae lodge in the brain, often causingepilepsy and death.2The difficulties in distinguishing members of the taeniid group of

cestodes are well recognised.3 Morphological procedures are

imperfect for human taeniids because the scolex is rarely voided andthe diagnosis has to rely on one or a few expelled proglottids whichmay be poorly preserved. When suspected cases have been treated(eg, with praziquantel) morphological characters such as thestructure of the ovary and the number of uterine branches are likelyto be unreliable. Inter-species differences can be detected

biochemically (eg, by electrophoresis of total proteins° and enzymeelectrophoresis5,6). The electrophoretic patterns are difficult tointerpret, and the parasite material has to be immediately processed