320
infant received rabies vaccine from birth and her antibody response to tissue culture rabies vaccine was in accord with the World Health Organisation recommendation’ of a minimum antibody concentration of 05 IU/ml for pre-exposure prophylaxis. Rabies antiserum was not given in this case. Department of Paediatrics, Khon Kaen University, Khon Kaen 40002, Thailand
PAGAKRONG LUMBIGANON
Department of Microbiology, Siriraj Hospital, Mahidol University, Bangkok
CHANTAPONG WASI
1.
Thongcharoen P.
Rabies in Asia and in Thailand. In. Thongcharoen P, Kurstak E, eds. Virus diseases in Asia: proceedings of the First International Conference on the Impact of Viral Diseases on the Development of Asian Countries Bangkok (Dec 7-13, 1986). Bangkok: Aksornsmai, 1988: 63-72. 2. Sipahioglu-U Alpaut S. Transplacental rabies in humans. Mikrobiyol Bull 1985; 19: 95-99. 3. Helmick CG, Tauxe RV, Vernon AA. Is there a risk to contacts of patients with rabies? Rev Inf Dis 1987; 9: 511-18. 4. Working Group II. Vaccine potency requirements for reduced immunization schedules and pre-exposure treatment. Dev Biol Stand 1978; 40: 268-70.
Paramyosin
as
helminth vaccine candidate
SiR,—To Professor Playfair and colleagues’ review of vaccines for helminth infestations (May 26, p 1263) I would add that the invertebrate muscle protein paramyosin has gained attention lately as a vaccine candidate for schistosorniasisl.2 and filariasis.3°’ For the past five decades, structural and functional studies on paramyosin have tended to concentrate on a few species of molluscs and arthropods.5 The first report of isolation of paramyosin from a platyhelminth appeared only in 1976. However, Matsumoto et al6 have demonstrated that paramyosin exists predominantly in schistosome tegument in a non-filamentous form as membranebounded elongated bodies. This evidence that paramyosin forms a significant component of the antigenic coat strengthens its case as a plausible vaccine candidate. Department of Physiological Biochemistry, Medical College of Pennsylvania, Philadelphia, Pennsylvania 19129, USA
Symptoms of reactogenicity in field trial of oral cholera vaccine SIR,-Clemens et all reported a three-year follow-up of a large field trial of two oral vaccines against cholera. This trial in Bangladesh was a great accomplishment, and the vaccines proved better than previous ones. Approval of the trial and the recruitment of 89 596 volunteers2 were based on a pilot study of 1257 people.3 There are two reasons why Clemens and his co-workers should not assume from their data that there is no reactogenicity of the product test3 two groups were given oral cholera vaccines, a third group received killed cells of Esherichia coli as placebo, and a fourth "plain water". In all four groups, however, the drink also contained bicarbonate as antacid together with lactate.’ Observed symptoms could therefore have resulted from such constituents present in the vaccines, placebo, and water. Thus, of 1257 subjects ingesting lactate and bicarbonate, 189 (15%) had
reactogenicity
four weeks apart. If of short duration, such reactions may be regarded as mild, and therefore acceptable. It is, however, their occurrence in the third and fourth test groups, that led Clemens et al from the mathematically correct conclusion that "the four groups exhibit no statistical difference in occurrence of symptoms" to the premature judgment that vaccines and placebo "can be given on three successive occasions without side-effects to persons greater than one 3 year of age" If the results truly represent a general appearance of such symptoms in the district, a chi-square analysis does not indicate nil reactogenicity. Clemens and colleagues’ data3 indicate only that the frequency of pain reactions due to immunisation is expected to be less than, for example, 3-4% at a statistical power of 80%. In the main trial 62 285 people completed the whole immunisation programme of three successive dosesand there were many references to protests. All subjective experiences of uncertain cause should be of concern. How they are handled in the Bangladesh study, and the part played by the denial of possible side-effects, are ethical issues that need elucidation. As Byrne says, "The end of medical ethics is to make clinical research self regulating in order to avoid disrepute for inexperience, haste and poor judgment".5 were
Skeppargatan 58, S-11459 Stockholm, Sweden
BORJE MARKMAN
1. Clemens JD, Sack D, Harris JR, et al. Field trial of oral cholera vaccines in
Bangladesh.
results from three-year follow-up. Lancet 1990; 335: 270-73. 2. Clemens JD, Sack DA, Harris JR, et al. Impact of B subunit killed whole-cell and killed whole-cell-only killed oral vaccines against cholera upon treated diarrheal illness and mortality in an area endemic for cholera. Lancet 1988; i: 1375-79. 3. Clemens JD, Stanton BF, Chakraborty J, et al. B subunit-whole cell and whole cell-only oral vaccines against cholera studies on reactogenicity and 4 5
immunogenicity. J Infect Dis 1987; 155: 79-85. Wigzell H. In: Applications to the Department of Drugs, the National Board of Health and Welfare. Stockholm: SBL, 1989. Byrne P. A European perspective in regulating clinical research: Britain needs a national ethical committee. Br Med J 1989; 299: 218.
Significance of crystal clear urine
SACHI SRI KANTHA
1. Lanar DE, Pearce EJ, James SL, Sher A. Identification of paramyosin as schistosome antigen recognized by intradermally vaccinated mice. Science 1986; 234: 593-96. 2. Pearce EJ, James SL, Hieny S, Lanar DE, Sher A. Induction of protective immunity against Schistosoma mansoni by vaccination with schistosome paramyosin (Sm 97), a non surface parasite antigen. Proc Natl Acad Sci ( USA ) 1988; 85: 5678-82. 3. Nanduri J, Kazura JW. Paramyosin-enhanced clearance of Brugia malayi microfilaremia in mice. J Immunol 1989; 143: 3359-63. 4. Limberger RJ, McReynolds LA. Filanal paramyosin: cDNA sequences from Dirofilaria immitis and Onchocerca volvulus. Mol Biochem Parasitol 1990; 38: 271-80. 5. Sn Kantha S, Watabe S, Hashimoto K. Comparative biochemistry of paramyosin: a review. J Food Biochem 1990; 14: 61-88. 6. Matsumoto Y, Perry G, Levine RJC, Mahmoud AAF, Ikawa M. Paramyosin and actin in schistosomal teguments. Nature 1988; 333: 76-78.
tested. In the
pain, 142 (11%) diarrhoea, and 60 (5%) nauseaSimilar frequencies also occurred after the second and third doses, which
SIR,-Dr Rawal and colleagues (May 19, p 1228) report that in children crystal clear urine, specimens were not infected and thus could be discarded without culture. If such a finding were confirmed substantial savings could be made. As part of a prospective study on urinary tract infection (UTI) in adults we studied the visual appearance of urine samples and its relation with both a dipstick method and microscopic examination with culture. Consecutive midstream urine specimens were obtained from 134 inpatients (mean age 55 years, range 17-100) at a department of internal medicine. 71 patients were female. Immediately after collection, urine specimens were examined by a nurse and classified as clear or cloudy. Specimens were then studied at the bedside with dipsticks and the ‘Clinitek System’ phonometer (Miles). After that, samples were sent to the microbiological laboratory for direct microscopy and culture. For 48 samples turbidity was assessed in the microbiological laboratory in a blinded fashion. UTI was defined by more than 100 000 colony-forming units (CFU)/mlof the same organism in pure culture in association with pyuria (8 or more
Ieucocytes/p.1).
The agreement between nurses and bacteriological laboratory assistants with respect to urine turbidity was perfect, with a kappa of 1. The prevalence of UTI was 10.4% (14/134). 107 (80%) urine specimens were clear and 27 were cloudy. Of the 107 clear samples, 4 were infected (as defined). The efficacy of visual inspection of
urinary samples was: sensitivity 71%, specificity 86%, positive predictive value 37%, negative predictive value 96%. In all the 4 infected urine specimens classified as clear (29% of UTI) the bedside dipstick study disclosed evidence of leucocytes or nitrites; a combination of turbidity assessment and dipstick testing for leucocytes and nitrites thus had a negative predictive value of 100%. Although the urinary turbidity can be easily assessed at bedside our study findings in adults do not support the results of Rawal et al.
infant received rabies vaccine from birth and her antibody response to tissue culture rabies vaccine was in accord with the World Health Organisation recommendation’ of a minimum antibody concentration of 05 IU/ml for pre-exposure prophylaxis. Rabies antiserum was not given in this case. Department of Paediatrics, Khon Kaen University, Khon Kaen 40002, Thailand
PAGAKRONG LUMBIGANON
Department of Microbiology, Siriraj Hospital, Mahidol University, Bangkok
CHANTAPONG WASI
1.
Thongcharoen P.
Rabies in Asia and in Thailand. In. Thongcharoen P, Kurstak E, eds. Virus diseases in Asia: proceedings of the First International Conference on the Impact of Viral Diseases on the Development of Asian Countries Bangkok (Dec 7-13, 1986). Bangkok: Aksornsmai, 1988: 63-72. 2. Sipahioglu-U Alpaut S. Transplacental rabies in humans. Mikrobiyol Bull 1985; 19: 95-99. 3. Helmick CG, Tauxe RV, Vernon AA. Is there a risk to contacts of patients with rabies? Rev Inf Dis 1987; 9: 511-18. 4. Working Group II. Vaccine potency requirements for reduced immunization schedules and pre-exposure treatment. Dev Biol Stand 1978; 40: 268-70.
Paramyosin
as
helminth vaccine candidate
SiR,—To Professor Playfair and colleagues’ review of vaccines for helminth infestations (May 26, p 1263) I would add that the invertebrate muscle protein paramyosin has gained attention lately as a vaccine candidate for schistosorniasisl.2 and filariasis.3°’ For the past five decades, structural and functional studies on paramyosin have tended to concentrate on a few species of molluscs and arthropods.5 The first report of isolation of paramyosin from a platyhelminth appeared only in 1976. However, Matsumoto et al6 have demonstrated that paramyosin exists predominantly in schistosome tegument in a non-filamentous form as membranebounded elongated bodies. This evidence that paramyosin forms a significant component of the antigenic coat strengthens its case as a plausible vaccine candidate. Department of Physiological Biochemistry, Medical College of Pennsylvania, Philadelphia, Pennsylvania 19129, USA
Symptoms of reactogenicity in field trial of oral cholera vaccine SIR,-Clemens et all reported a three-year follow-up of a large field trial of two oral vaccines against cholera. This trial in Bangladesh was a great accomplishment, and the vaccines proved better than previous ones. Approval of the trial and the recruitment of 89 596 volunteers2 were based on a pilot study of 1257 people.3 There are two reasons why Clemens and his co-workers should not assume from their data that there is no reactogenicity of the product test3 two groups were given oral cholera vaccines, a third group received killed cells of Esherichia coli as placebo, and a fourth "plain water". In all four groups, however, the drink also contained bicarbonate as antacid together with lactate.’ Observed symptoms could therefore have resulted from such constituents present in the vaccines, placebo, and water. Thus, of 1257 subjects ingesting lactate and bicarbonate, 189 (15%) had
reactogenicity
four weeks apart. If of short duration, such reactions may be regarded as mild, and therefore acceptable. It is, however, their occurrence in the third and fourth test groups, that led Clemens et al from the mathematically correct conclusion that "the four groups exhibit no statistical difference in occurrence of symptoms" to the premature judgment that vaccines and placebo "can be given on three successive occasions without side-effects to persons greater than one 3 year of age" If the results truly represent a general appearance of such symptoms in the district, a chi-square analysis does not indicate nil reactogenicity. Clemens and colleagues’ data3 indicate only that the frequency of pain reactions due to immunisation is expected to be less than, for example, 3-4% at a statistical power of 80%. In the main trial 62 285 people completed the whole immunisation programme of three successive dosesand there were many references to protests. All subjective experiences of uncertain cause should be of concern. How they are handled in the Bangladesh study, and the part played by the denial of possible side-effects, are ethical issues that need elucidation. As Byrne says, "The end of medical ethics is to make clinical research self regulating in order to avoid disrepute for inexperience, haste and poor judgment".5 were
Skeppargatan 58, S-11459 Stockholm, Sweden
BORJE MARKMAN
1. Clemens JD, Sack D, Harris JR, et al. Field trial of oral cholera vaccines in
Bangladesh.
results from three-year follow-up. Lancet 1990; 335: 270-73. 2. Clemens JD, Sack DA, Harris JR, et al. Impact of B subunit killed whole-cell and killed whole-cell-only killed oral vaccines against cholera upon treated diarrheal illness and mortality in an area endemic for cholera. Lancet 1988; i: 1375-79. 3. Clemens JD, Stanton BF, Chakraborty J, et al. B subunit-whole cell and whole cell-only oral vaccines against cholera studies on reactogenicity and 4 5
immunogenicity. J Infect Dis 1987; 155: 79-85. Wigzell H. In: Applications to the Department of Drugs, the National Board of Health and Welfare. Stockholm: SBL, 1989. Byrne P. A European perspective in regulating clinical research: Britain needs a national ethical committee. Br Med J 1989; 299: 218.
Significance of crystal clear urine
SACHI SRI KANTHA
1. Lanar DE, Pearce EJ, James SL, Sher A. Identification of paramyosin as schistosome antigen recognized by intradermally vaccinated mice. Science 1986; 234: 593-96. 2. Pearce EJ, James SL, Hieny S, Lanar DE, Sher A. Induction of protective immunity against Schistosoma mansoni by vaccination with schistosome paramyosin (Sm 97), a non surface parasite antigen. Proc Natl Acad Sci ( USA ) 1988; 85: 5678-82. 3. Nanduri J, Kazura JW. Paramyosin-enhanced clearance of Brugia malayi microfilaremia in mice. J Immunol 1989; 143: 3359-63. 4. Limberger RJ, McReynolds LA. Filanal paramyosin: cDNA sequences from Dirofilaria immitis and Onchocerca volvulus. Mol Biochem Parasitol 1990; 38: 271-80. 5. Sn Kantha S, Watabe S, Hashimoto K. Comparative biochemistry of paramyosin: a review. J Food Biochem 1990; 14: 61-88. 6. Matsumoto Y, Perry G, Levine RJC, Mahmoud AAF, Ikawa M. Paramyosin and actin in schistosomal teguments. Nature 1988; 333: 76-78.
tested. In the
pain, 142 (11%) diarrhoea, and 60 (5%) nauseaSimilar frequencies also occurred after the second and third doses, which
SIR,-Dr Rawal and colleagues (May 19, p 1228) report that in children crystal clear urine, specimens were not infected and thus could be discarded without culture. If such a finding were confirmed substantial savings could be made. As part of a prospective study on urinary tract infection (UTI) in adults we studied the visual appearance of urine samples and its relation with both a dipstick method and microscopic examination with culture. Consecutive midstream urine specimens were obtained from 134 inpatients (mean age 55 years, range 17-100) at a department of internal medicine. 71 patients were female. Immediately after collection, urine specimens were examined by a nurse and classified as clear or cloudy. Specimens were then studied at the bedside with dipsticks and the ‘Clinitek System’ phonometer (Miles). After that, samples were sent to the microbiological laboratory for direct microscopy and culture. For 48 samples turbidity was assessed in the microbiological laboratory in a blinded fashion. UTI was defined by more than 100 000 colony-forming units (CFU)/mlof the same organism in pure culture in association with pyuria (8 or more
Ieucocytes/p.1).
The agreement between nurses and bacteriological laboratory assistants with respect to urine turbidity was perfect, with a kappa of 1. The prevalence of UTI was 10.4% (14/134). 107 (80%) urine specimens were clear and 27 were cloudy. Of the 107 clear samples, 4 were infected (as defined). The efficacy of visual inspection of
urinary samples was: sensitivity 71%, specificity 86%, positive predictive value 37%, negative predictive value 96%. In all the 4 infected urine specimens classified as clear (29% of UTI) the bedside dipstick study disclosed evidence of leucocytes or nitrites; a combination of turbidity assessment and dipstick testing for leucocytes and nitrites thus had a negative predictive value of 100%. Although the urinary turbidity can be easily assessed at bedside our study findings in adults do not support the results of Rawal et al.
