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Mannose-binding lectin
CORRESPONDENCE
Since the early 1900s the coincidence of these epidemics with dry dusty conditions has prompted the suggestion that they are associated. Low absolute humidity and increasing intensity of the Harmattan during an epidemic in northern Nigeria were correlated with a rise in hospital admissions for meningococcal meningitis 1 month later.2 In Benin, a substantial proportion of the temporal variability in cases of disease was attributed to the same factors.3 Changes in the ratio of clinical to subclinical infection, rather than in the risk of infection, may explain the seasonal distribution of meningitis, with risk factors for overt disease more extreme in epidemic than in nonepidemic years. Systemic infection via the nasopharyngeal mucosa causes invasive disease, and low absolute humidity and atmospheric dust might increase mucosal invasion of the meningococcus in infected people by damaging the mucosal barrier or inhibiting its immune defence.2 Cases of meningococcal disease have been similarly associated with aerosols through exposure to dusty work environments and cigarette smoke.4 The association of epidemics with low absolute humidity and dust is supported by observations that epidemics have been reported following drought years and in dry, dusty conditions, and rarely occur where there is dense forest. Moreover, evidence suggests that dust inhibits precipitation, thereby exacerbating the intensity and spread of drought conditions. The factors leading to desertification in the Sahel have contributed to the increased dustiness of the environment and have been implicated in the recent appearance of epidemics in unusual areas.5 Assessment of the contribution of low absolute humidity and dust as risk factors for meningococcal meningitis is an objective of the Meningitis Forecasting Project. In the absence of detailed ground-based meteorological data in Africa, satellite images of rainfall estimates and absorbing aerosols allow proxy near real-time monitoring of these environmental variables. Although other non-environmental factors are also likely to be important, the potential for epidemic early warning and response is significant, and highlights the need for environmental monitoring alongside improved disease surveillance in epidemic-susceptible parts of Africa. Anna M Molesworth, Luis E Cuevas, Andrew P Morse, Jay R Herman, *Madeleine C Thomson Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK
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McCarthy M. Dust Clouds implicated in spread of infection. Lancet 2001; 358: 478. Greenwood BM, Blakebrough IS, Bradley AK, Wali S, Whittle HC. Meningococcal disease and season in subsaharan Africa. Lancet 1984; 326: 1339–42. Besancenot JP, Boko M, Oke PC. Weather conditions and cereobrospinal meningitis in Benin (Gulf of Guinea, West Africa). Eur J Epidemiol 1997; 13: 807–15. Stanwell-Smith RE, Stuart JM, Hughes AO, Robinson P, Griffin MB, Cartwright K. Smoking, the environment and meningococcal disease: a case control study. Epidemiol Infect 1994; 112: 315–28. Rosenfeld D, Rudich Y, Lahav R. Desert dust suppressing precipitation: a possible desertification feedback loop. Proc Natl Acad Sci USA 2001; 98: 5975–80.
Mannose-binding lectin Sir—R Alan and B Ezekowitz, in their Aug 25 commentary,1 discuss two excellent reports (one from my exdepartment) showing that this opsonisation defect predicts trouble with infection in patients made neutropenic by cytotoxic drugs given for malignant disorders. They adopt a quaint historical approach and we learn too little from history, but the history must be right. Clinical research is unfashionable, and grossly inadequately supported now, but it is the source of most important medical advances. Wright, I think, not Metchnikov, described opsonisation, at first a function of antibodies, and produced the term—brilliantly translated by Bernard Shaw as buttering in Doctors’ Dilemma. Miller showed an antibodyindependent defect of yeast opsonisation in two families, and Betty Harvey and I showed that this defect occurred in about one in 20 of the population and was associated with frequent unexplained infection, diarrhoea, and atopy in small children, and also good health. We showed that it was one defect by sample mixing experiments and that normal serum corrected it, so it was not an inhibitor. The range of symptoms needs explaining and association with neutropenia in these reports is another example of the interaction with other imunodeficiencies already described. Both Miller and us showed (not in a trial) that plasma infusion corrected the defect, and improved the patients. I handed such sera to several laboratories for identification of the defect, and our laboratory (Turner and Super) showed that it was mannose-binding protein. Alan and Ezekovtiz end with the sentence “In the longer term, replacement treatment is a tantalising possibility,” but it has already been achieved. Perhaps the identification of
the defect and the fascinating genetics will be useful; perhaps purified, or better genetically engineered human mannose-binding protein produced in vitro will be cheaper, better, and safer than plasma. As usual in medicine, however, the useful part was achieved by good clinical research using simple function tests. J F Soothill Pensylvania, Lodge Lane, Axminster, Devon EX13 5RT, UK 1
Alan R, Ezekowitz B. Mannose-binding lectin in prediction of susceptiblity to infection. Lancet 2001; 358: 598–99.
Sir—We are displeased to note that a change in terminology was made, without our knowledge, to the printed version of our report (Aug 25, p 637)1 on mannan-binding lectin, in which mannan-binding lectin was changed to mannose-binding lectin. I feel strongly about this terminology.1 I object to the change from mannanbinding to mannose-binding lectin that has been introduced into AngloAmerican reports. The protein was discovered in 1978 in Japan by Kawasaki and co-workers,2 and named mannan-binding protein because of its affinity for mannan, a yeast glycoprotein. They published several reports on this protein in the following years. Townsend and Stahl3 later gave the same protein a more biochemically correct name, mannose/ N-acetylglucosamine/fucose binding protein. The term, oddly enough, did not stick. In 1983, the term mannosebinding protein was introduced by Wild and colleagues.4 The research done by the Japanese groups working on mannan-binding protein was outstanding from the very start, and we are fortunate indeed that excellent work on this protein continues to emerge from Japan. I find it not only unsavoury to rename, for no apparent reason, a protein discovered by others, but also misleading in the present case, since mannan-binding lectin reacts just as well with several monosaccharides other than mannose. The term lectin, instead of protein was very properly introduced much to avoid confusing the later5 abbreviation MBP with the same one shared by other proteins. Jens C Jensenius Department of Medical Microbiology and Immunology, University of Aarhus, DK-8000 Aarhus, Denmark (e-mail: [email protected]) 1
Peterslund NA, Koch C, Jensenius JC, Thiel S. Association between deficiency of mannose-binding lectin and severe infections
THE LANCET • Vol 359 • January 5, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Since the early 1900s the coincidence of these epidemics with dry dusty conditions has prompted the suggestion that they are associated. Low absolute humidity and increasing intensity of the Harmattan during an epidemic in northern Nigeria were correlated with a rise in hospital admissions for meningococcal meningitis 1 month later.2 In Benin, a substantial proportion of the temporal variability in cases of disease was attributed to the same factors.3 Changes in the ratio of clinical to subclinical infection, rather than in the risk of infection, may explain the seasonal distribution of meningitis, with risk factors for overt disease more extreme in epidemic than in nonepidemic years. Systemic infection via the nasopharyngeal mucosa causes invasive disease, and low absolute humidity and atmospheric dust might increase mucosal invasion of the meningococcus in infected people by damaging the mucosal barrier or inhibiting its immune defence.2 Cases of meningococcal disease have been similarly associated with aerosols through exposure to dusty work environments and cigarette smoke.4 The association of epidemics with low absolute humidity and dust is supported by observations that epidemics have been reported following drought years and in dry, dusty conditions, and rarely occur where there is dense forest. Moreover, evidence suggests that dust inhibits precipitation, thereby exacerbating the intensity and spread of drought conditions. The factors leading to desertification in the Sahel have contributed to the increased dustiness of the environment and have been implicated in the recent appearance of epidemics in unusual areas.5 Assessment of the contribution of low absolute humidity and dust as risk factors for meningococcal meningitis is an objective of the Meningitis Forecasting Project. In the absence of detailed ground-based meteorological data in Africa, satellite images of rainfall estimates and absorbing aerosols allow proxy near real-time monitoring of these environmental variables. Although other non-environmental factors are also likely to be important, the potential for epidemic early warning and response is significant, and highlights the need for environmental monitoring alongside improved disease surveillance in epidemic-susceptible parts of Africa. Anna M Molesworth, Luis E Cuevas, Andrew P Morse, Jay R Herman, *Madeleine C Thomson Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK
82
1 2
3
4
5
McCarthy M. Dust Clouds implicated in spread of infection. Lancet 2001; 358: 478. Greenwood BM, Blakebrough IS, Bradley AK, Wali S, Whittle HC. Meningococcal disease and season in subsaharan Africa. Lancet 1984; 326: 1339–42. Besancenot JP, Boko M, Oke PC. Weather conditions and cereobrospinal meningitis in Benin (Gulf of Guinea, West Africa). Eur J Epidemiol 1997; 13: 807–15. Stanwell-Smith RE, Stuart JM, Hughes AO, Robinson P, Griffin MB, Cartwright K. Smoking, the environment and meningococcal disease: a case control study. Epidemiol Infect 1994; 112: 315–28. Rosenfeld D, Rudich Y, Lahav R. Desert dust suppressing precipitation: a possible desertification feedback loop. Proc Natl Acad Sci USA 2001; 98: 5975–80.
Mannose-binding lectin Sir—R Alan and B Ezekowitz, in their Aug 25 commentary,1 discuss two excellent reports (one from my exdepartment) showing that this opsonisation defect predicts trouble with infection in patients made neutropenic by cytotoxic drugs given for malignant disorders. They adopt a quaint historical approach and we learn too little from history, but the history must be right. Clinical research is unfashionable, and grossly inadequately supported now, but it is the source of most important medical advances. Wright, I think, not Metchnikov, described opsonisation, at first a function of antibodies, and produced the term—brilliantly translated by Bernard Shaw as buttering in Doctors’ Dilemma. Miller showed an antibodyindependent defect of yeast opsonisation in two families, and Betty Harvey and I showed that this defect occurred in about one in 20 of the population and was associated with frequent unexplained infection, diarrhoea, and atopy in small children, and also good health. We showed that it was one defect by sample mixing experiments and that normal serum corrected it, so it was not an inhibitor. The range of symptoms needs explaining and association with neutropenia in these reports is another example of the interaction with other imunodeficiencies already described. Both Miller and us showed (not in a trial) that plasma infusion corrected the defect, and improved the patients. I handed such sera to several laboratories for identification of the defect, and our laboratory (Turner and Super) showed that it was mannose-binding protein. Alan and Ezekovtiz end with the sentence “In the longer term, replacement treatment is a tantalising possibility,” but it has already been achieved. Perhaps the identification of
the defect and the fascinating genetics will be useful; perhaps purified, or better genetically engineered human mannose-binding protein produced in vitro will be cheaper, better, and safer than plasma. As usual in medicine, however, the useful part was achieved by good clinical research using simple function tests. J F Soothill Pensylvania, Lodge Lane, Axminster, Devon EX13 5RT, UK 1
Alan R, Ezekowitz B. Mannose-binding lectin in prediction of susceptiblity to infection. Lancet 2001; 358: 598–99.
Sir—We are displeased to note that a change in terminology was made, without our knowledge, to the printed version of our report (Aug 25, p 637)1 on mannan-binding lectin, in which mannan-binding lectin was changed to mannose-binding lectin. I feel strongly about this terminology.1 I object to the change from mannanbinding to mannose-binding lectin that has been introduced into AngloAmerican reports. The protein was discovered in 1978 in Japan by Kawasaki and co-workers,2 and named mannan-binding protein because of its affinity for mannan, a yeast glycoprotein. They published several reports on this protein in the following years. Townsend and Stahl3 later gave the same protein a more biochemically correct name, mannose/ N-acetylglucosamine/fucose binding protein. The term, oddly enough, did not stick. In 1983, the term mannosebinding protein was introduced by Wild and colleagues.4 The research done by the Japanese groups working on mannan-binding protein was outstanding from the very start, and we are fortunate indeed that excellent work on this protein continues to emerge from Japan. I find it not only unsavoury to rename, for no apparent reason, a protein discovered by others, but also misleading in the present case, since mannan-binding lectin reacts just as well with several monosaccharides other than mannose. The term lectin, instead of protein was very properly introduced much to avoid confusing the later5 abbreviation MBP with the same one shared by other proteins. Jens C Jensenius Department of Medical Microbiology and Immunology, University of Aarhus, DK-8000 Aarhus, Denmark (e-mail: [email protected]) 1
Peterslund NA, Koch C, Jensenius JC, Thiel S. Association between deficiency of mannose-binding lectin and severe infections
THE LANCET • Vol 359 • January 5, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.