- Email: [email protected]
Self-use of rapid tests for malaria diagnosis
CORRESPONDENCE
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nimesulide as tocolytic. Lancet 1999; 354: 1615 (published erratum appears in Lancet 2000; 355: 238). Hawkey CJ. COX-2 inhibitors. Lancet 1999; 353: 307–14. Famaey JP. In vitro and in vivo pharmacological evidence of selective cyclooxygenase-2 inhibition by nimesulide: an overview. Inflamm Res 1997; 46: 437–46.
Self-use of rapid tests for malaria diagnosis Sir—In several European countries, rapid tests for malaria are marketed for self-use by tourists. Tomas Jelinek and colleagues (Nov 6, p 1609)1 describe the self-use of rapid tests for malaria diagnosis by European tourists in a holiday resort in Kenya. In a prospective survey of 98 febrile tourists (11 with falciparum malaria), only 67 were able to carry out the test correctly. Reasons for failure consisted of difficulties in handling of the test and in interpretation of test results. That only one of the patients with malaria was able to obtain a valid test result, whereas patients with other febrile causes were able to do the test substantially better, was attributed to more severe sickness of the malariaaffected patients. Since severity of sickness has an influence on test handling, it would have been interesting to know the performance of the test when done by healthy, inexperienced tourists on their sick fellow travellers. However, the investigators recommend the use of the rapid test only after appropriate instruction and training, and after travellers have completed the test procedure successfully. We agree with Jelinek and colleagues, but it is important to point out that successful handling of the test, despite its good sensitivity and specificity,2,3 does not guarantee correct results. We have described a severely ill patient who had a 30% falciparum parasitaemia.4 The rapid test, done by an experienced technician, gave a negative result. All immunological tests are hampered by the fact that a prozone event5 occurs at high antigen concentrations, which leads to falselow or false-negative results. Therefore, a 1 in 10 0·9% sodium chloride dilution of the sample was needed to obtain a correct positive result. If, in the endemic area, our patient had relied on the rapid test after correctly carrying out the analysis, delayed diagnosis with fatal outcome would have been the consequence. Fortunately, due to microscopic testing and immediate therapy, our patient survived.
THE LANCET • Vol 355 • January 15, 2000
Thus, in addition to the recommendation of Jelinek and colleagues, instructions to a traveller should not only include how to carry out a correct test, but should also include an explanation of the limits of the test (ie, impaired performance when done by severely sick or delirious patients, and the prozone event) and the appropriate actions to be taken, such as the recommendation of asking a healthy colleague to do the test, and the instruction of diluting a negative sample in the case of a severely sick patient.
sampling. Our study suggests that a user-friendly kit can be correctly implemented by travellers without training if the test system has been appropriately validated. The proposal that all travellers should receive instruction and training would reduce access to and increase cost of the selfdiagnostic kits and significantly restrict the benefit of this new technology for travellers at risk of malaria. It would be a pity to prevent the introduction of this kit because of a difficulty that could be rectified.
Lorenz Risch, Margrit Bader, *Andreas R Huber
*Hospital for Tropical Diseases, London WC1E 6AU, UK; and Infectious and Tropical Diseases, St Georges Hospital, London (e-mail: [email protected])
Department of Laboratory Medicine, Kantonsspital Aarau, 5001 Aarau, Switzerland (e-mail: [email protected])
*R H Behrens, C J M Whitty
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Jelinek T, Amsler L, Grobusch MP, Nothdurft HD. Self-use of rapid test for malaria diagnosis by tourists. Lancet 1999; 354: 1609. Van den Ende J, Veroort T, Van Gompel A, Lynen L. Evaluation of two tests based on the detection of histidine rich protein 2 for the diagnosis of imported Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg 1998; 92: 285–88. Jelinek T, Grobusch M, Schwenke S, et al. Sensitivity and specificity of dipstick test for the rapid diagnosis of malaria in non-immune travelers. J Clin Microbiol 1999; 37: 721–23. Risch L, Bader M, Huber AR. Falsch negativer Malaria-Schnelltest. Schweiz Med Wochenschr 1999; 129: 1002. Heidelberger M, Kendall FE. A quantitative theory of the precipitin reaction. J Exp Med 1935; 62: 697–720.
Sir—The high failure rate by travellers with malaria to correctly use immunochromatographic diagnostic kits to diagnose falciparum malaria is a major feature of Tomas Jelinek and colleagues study.1 A similar study of febrile patients who sought medical treatment from the Hospital for Tropical Diseases casualty unit was undertaken in London and found different results. 153 unsupervised and untrained travellers with malaria symptoms, who were quite ill, tested themselves for falciparum malaria with the test card. Only 14 (9%) failed to carry out a valid test (paper submitted). All 22 patients with falciparum malaria successfully completed the test, and compared with laboratory blood film findings, their interpretation of the test was 97% specific and 95% sensitive. The difference between our findings and the poor results from tourists in Kenya may be due to the poor quality of the manufacturer’s instruction sheet and our use of a customised test procedure. In our study we drafted the test instruction leaflet based on feedback from participants and carefully evaluated devices for use in blood
Jelinek T, Amsler L, Grobusch MP, Nothdurft HD. Self-use of rapid tests for malaria diagnosis by tourists. Lancet 1999; 354: 1609.
Extreme potency of botulinum toxin Sir—In his book review of Ken Alibek’s Biohazard, Jack Woodall (Oct 30, p 1568)1 attempts to correct the author by asserting that tetanus and Shiga toxins are four times more potent than botulinum neurotoxin in human beings. However, other reliable sources2,3 support Alibek’s statement that botulinum toxin is the most lethal natural poison known. The deadliness of these toxins for human beings can be extrapolated from findings in primates and other animals. Gill tabulated the parenteral median lethal dose (LD50) of botulinum toxin in monkeys to be as low as 0·4 ng/kg bodyweight for botulinum toxin versus 1 ng/kg for Shiga toxin.2 Parenteral LD50 for mice were calculated as low as 0·4 ng/kg for botulinum toxin, 1 ng/kg for tetanus toxin, and 450–1300 ng/kg for Shiga toxin.2 The US Army lists the parenteral mouse LD50 of botulinum toxin as 1 ng/kg, and of shiga and tetanus toxins as 2 ng/kg.3 The potency of botulinum toxin is accentuated when calculated on a molar basis because Shiga toxin (55 kD) is about a third the molecular weight of botulinum toxin (150 kD).3 Although a debate over which toxin is most deadly may seem needlessly morbid and academic, those who choose to develop and use biological weapons pay close attention to these calculations. The Iraqi government admitted to the United Nations Special Commission on Monitoring to having armed missiles and artillery shells with at least 10 000 L of botulinum toxin, more than anthrax, aflatoxin, or any
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nimesulide as tocolytic. Lancet 1999; 354: 1615 (published erratum appears in Lancet 2000; 355: 238). Hawkey CJ. COX-2 inhibitors. Lancet 1999; 353: 307–14. Famaey JP. In vitro and in vivo pharmacological evidence of selective cyclooxygenase-2 inhibition by nimesulide: an overview. Inflamm Res 1997; 46: 437–46.
Self-use of rapid tests for malaria diagnosis Sir—In several European countries, rapid tests for malaria are marketed for self-use by tourists. Tomas Jelinek and colleagues (Nov 6, p 1609)1 describe the self-use of rapid tests for malaria diagnosis by European tourists in a holiday resort in Kenya. In a prospective survey of 98 febrile tourists (11 with falciparum malaria), only 67 were able to carry out the test correctly. Reasons for failure consisted of difficulties in handling of the test and in interpretation of test results. That only one of the patients with malaria was able to obtain a valid test result, whereas patients with other febrile causes were able to do the test substantially better, was attributed to more severe sickness of the malariaaffected patients. Since severity of sickness has an influence on test handling, it would have been interesting to know the performance of the test when done by healthy, inexperienced tourists on their sick fellow travellers. However, the investigators recommend the use of the rapid test only after appropriate instruction and training, and after travellers have completed the test procedure successfully. We agree with Jelinek and colleagues, but it is important to point out that successful handling of the test, despite its good sensitivity and specificity,2,3 does not guarantee correct results. We have described a severely ill patient who had a 30% falciparum parasitaemia.4 The rapid test, done by an experienced technician, gave a negative result. All immunological tests are hampered by the fact that a prozone event5 occurs at high antigen concentrations, which leads to falselow or false-negative results. Therefore, a 1 in 10 0·9% sodium chloride dilution of the sample was needed to obtain a correct positive result. If, in the endemic area, our patient had relied on the rapid test after correctly carrying out the analysis, delayed diagnosis with fatal outcome would have been the consequence. Fortunately, due to microscopic testing and immediate therapy, our patient survived.
THE LANCET • Vol 355 • January 15, 2000
Thus, in addition to the recommendation of Jelinek and colleagues, instructions to a traveller should not only include how to carry out a correct test, but should also include an explanation of the limits of the test (ie, impaired performance when done by severely sick or delirious patients, and the prozone event) and the appropriate actions to be taken, such as the recommendation of asking a healthy colleague to do the test, and the instruction of diluting a negative sample in the case of a severely sick patient.
sampling. Our study suggests that a user-friendly kit can be correctly implemented by travellers without training if the test system has been appropriately validated. The proposal that all travellers should receive instruction and training would reduce access to and increase cost of the selfdiagnostic kits and significantly restrict the benefit of this new technology for travellers at risk of malaria. It would be a pity to prevent the introduction of this kit because of a difficulty that could be rectified.
Lorenz Risch, Margrit Bader, *Andreas R Huber
*Hospital for Tropical Diseases, London WC1E 6AU, UK; and Infectious and Tropical Diseases, St Georges Hospital, London (e-mail: [email protected])
Department of Laboratory Medicine, Kantonsspital Aarau, 5001 Aarau, Switzerland (e-mail: [email protected])
*R H Behrens, C J M Whitty
1 1
2
3
4
5
Jelinek T, Amsler L, Grobusch MP, Nothdurft HD. Self-use of rapid test for malaria diagnosis by tourists. Lancet 1999; 354: 1609. Van den Ende J, Veroort T, Van Gompel A, Lynen L. Evaluation of two tests based on the detection of histidine rich protein 2 for the diagnosis of imported Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg 1998; 92: 285–88. Jelinek T, Grobusch M, Schwenke S, et al. Sensitivity and specificity of dipstick test for the rapid diagnosis of malaria in non-immune travelers. J Clin Microbiol 1999; 37: 721–23. Risch L, Bader M, Huber AR. Falsch negativer Malaria-Schnelltest. Schweiz Med Wochenschr 1999; 129: 1002. Heidelberger M, Kendall FE. A quantitative theory of the precipitin reaction. J Exp Med 1935; 62: 697–720.
Sir—The high failure rate by travellers with malaria to correctly use immunochromatographic diagnostic kits to diagnose falciparum malaria is a major feature of Tomas Jelinek and colleagues study.1 A similar study of febrile patients who sought medical treatment from the Hospital for Tropical Diseases casualty unit was undertaken in London and found different results. 153 unsupervised and untrained travellers with malaria symptoms, who were quite ill, tested themselves for falciparum malaria with the test card. Only 14 (9%) failed to carry out a valid test (paper submitted). All 22 patients with falciparum malaria successfully completed the test, and compared with laboratory blood film findings, their interpretation of the test was 97% specific and 95% sensitive. The difference between our findings and the poor results from tourists in Kenya may be due to the poor quality of the manufacturer’s instruction sheet and our use of a customised test procedure. In our study we drafted the test instruction leaflet based on feedback from participants and carefully evaluated devices for use in blood
Jelinek T, Amsler L, Grobusch MP, Nothdurft HD. Self-use of rapid tests for malaria diagnosis by tourists. Lancet 1999; 354: 1609.
Extreme potency of botulinum toxin Sir—In his book review of Ken Alibek’s Biohazard, Jack Woodall (Oct 30, p 1568)1 attempts to correct the author by asserting that tetanus and Shiga toxins are four times more potent than botulinum neurotoxin in human beings. However, other reliable sources2,3 support Alibek’s statement that botulinum toxin is the most lethal natural poison known. The deadliness of these toxins for human beings can be extrapolated from findings in primates and other animals. Gill tabulated the parenteral median lethal dose (LD50) of botulinum toxin in monkeys to be as low as 0·4 ng/kg bodyweight for botulinum toxin versus 1 ng/kg for Shiga toxin.2 Parenteral LD50 for mice were calculated as low as 0·4 ng/kg for botulinum toxin, 1 ng/kg for tetanus toxin, and 450–1300 ng/kg for Shiga toxin.2 The US Army lists the parenteral mouse LD50 of botulinum toxin as 1 ng/kg, and of shiga and tetanus toxins as 2 ng/kg.3 The potency of botulinum toxin is accentuated when calculated on a molar basis because Shiga toxin (55 kD) is about a third the molecular weight of botulinum toxin (150 kD).3 Although a debate over which toxin is most deadly may seem needlessly morbid and academic, those who choose to develop and use biological weapons pay close attention to these calculations. The Iraqi government admitted to the United Nations Special Commission on Monitoring to having armed missiles and artillery shells with at least 10 000 L of botulinum toxin, more than anthrax, aflatoxin, or any
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