- Email: [email protected]
Hepatitis C virus in people with HIV infection
CORRESPONDENCE
response (>40%) and of long-term disease-free survival (>10%, with follow-up >7 years). Moreover, after possible recurrence, the tumour should be retyped for TP53 status and, if mutated, the patient could be treated with paclitaxel. Such an approach to chemotherapy of ovarian carcinoma could allow delivery of optimum doses of the most effective single agent, avoiding the toxic effects expected by combination therapy. *Silvana Pilotti, Maria Oggionni, Silvia Böhm, Marco A Pierotti, Franco Zunino *Departments of Pathology, Experimental Oncology, and Preventive Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via G Venezian, 1-20133, Milan, Italy (e-mail: [email protected]) 1
2
3
4
5
The International Collaborative Ovarian Neoplasm (ICON) Group. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet 2002, 360: 505–15. Lavarino C, Pilotti S, Oggionni M, et al. P53 gene status and response to platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma. J Clin Oncol 2000; 18: 3936–45. Righetti SC, Della Torre G, Pilotti S, et al. A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma. Cancer Res 1996; 56: 689–93. Johnstone RW, Ruefli AA, Lowe SW. Apoptosis: a link between cancer genetics and chemotherapy. Cell 2002; 108: 153–64. Bohm S, Oriana S, Spatti G, et al. Dose intensification of platinum compounds with glutathione protection as induction chemotherapy for advanced ovarian carcinoma. Oncology 1999; 57: 115–20.
Authors’ reply Sir—We do not agree with the suggestions by Robert Ozols and colleagues that the results of GOG111 and OV10 are more believable than ours because these trials were done in a well defined population. ICON3 was a large randomised trial with simple outcome measures done in a population of women who are generally treated with chemotherapy for ovarian cancer. The suggestion by Ozols that the dose of carboplatin could explain our results is implausible, because the same carboplatin regimens were used in the control arm and the test arm; the test arm differed only by addition of paclitaxel to standard platinumbased chemotherapy. Furthermore, although we do not favour making direct comparisons of survival between trials, it should be noted that patients in both the control and
2088
research arms in ICON3 had very good outcome by any standard (median survival 36 months). The fact that ICON3 was large allowed us to do exploratory analyses by stage, residual bulk, histological type, differentiation, and age. This ability should be seen as the strength of a large trial rather than as a weakness, as suggested by Ozols. Both Earl and Ozols offer some suggestions to explain our results. In a systematic review1 of all relevant trials, these and other explanations have been considered to see whether they explain the clear conflict between positive (GOG111, OV10) and negative (GOG132 and ICON3) trials. In this review, trials were grouped by similarity of research regimens, similarity of control regimens, type of patients enrolled, and extent of crossover before progression. The results clearly showed that the broad entry criteria in ICON3 were not the reason for the discrepant results and, in particular, that considering only patients with bulky residual disease did not explain the conflicting results. Further, the suggestion that early use of other therapies in some trials may explain the results does not hold. Of the four explanations looked at, the only one that accorded with the results was the control regimen used. In particular, the two positive trials used the regimen of cyclophosphamide (750 mg/m2) and cisplatin (75 mg/m2) for their control arm. The review also examined external evidence, which lends support to this explanation.2 We should emphasise that ICON3 was not done or published to deny patients treatment or to claim that any other trials “got it wrong”. In our opinion, to present and discuss conflicting and complex data is important, however difficult that might be, so that patients and physicians can make informed choices about the true benefits of these chemotherapy regimens and, as Pilotti and colleagues point out, to motivate further research to improve outcomes for patients with ovarian cancer.
cisplatin chemotherapy of ovarian carcinoma: a meta-analysis. J Clin Oncol 1991; 9: 1668–74.
Hepatitis C virus in people with HIV infection Sir—In his Commentary, Andrew Talal (Aug 24, p 584) 1 defines hepatitis C virus (HCV) as an “opportunistic infection” when it occurs in individuals already infected with HIV. Although not new—M Sulkowski and colleagues2 use the same term—this definition is incorrect. An infection can be defined as opportunistic only when it causes no pathology in immunocompetent individuals and provokes serious organ damage in immunosuppressed patients, or when, as D Relman and S Falkow3 describe, “disease is a rare consequence of the host-microbe encounter”. These criteria clearly do not apply to HCV infection. Talal fails to account for two important issues. The first is the role of alcohol in progression of HCV infection in HIV-coinfected patients. This issue is important because many patients with HCV and HIV infection are injecting drug users who also misuse alcohol. Indeed, Benhamou and co-workers4 found that alcohol was an important factor in progression of hepatitis C to cirrhosis in HIV-coinfected patients. Secondly, the observation by Benhamou and colleagues5 that progression to cirrhosis is increased in patients with low CD4 cell-counts, implies that antiretroviral therapy per se can substantially slow such progression.5 Talal makes no mention of successful HIV treatment combined with reduction of alcohol intake to control progression of HCV-induced liver damage. This approach should be considered before rushing to use interferon and ribavirin, which is a combination therapy that has side-effects, potentially harmful interactions with antiretroviral drugs, and a still unsatisfying success rate. Sandro Vento Section of Infectious Diseases, Department of Pathology, University of Verona, 37138 Verona, Italy (e-mail: [email protected])
*Mahesh Parmar, Peter Harper, Nicoletta Colombo, Valter Torri, David Guthrie, on behalf of the ICON3 collaborators
1
MRC Clinical Trials Unit, London NWI 2DA, UK (e-mail: [email protected])
2
1
2
Sandercock J, Parmar MKB, Torri V, Qian W. Firstline treatment for advanced ovarian cancer: paclitaxel, platinum and the evidence. Br J Cancer 2002; 87: 815–24. Ovarian Cancer Meta-analysis Project. Cyclophosphamide plus cisplatin versus cyclophosphamide, doxorubicin and
3
Talal A. Opportunistic infections in HIVinfected individuals: hepatitis C virus. Lancet 2002; 360: 584–86. Sulkowski MS, Mast EE, Seeff LB, Thomas DL. Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus. Clin Infect Dis 2000; 30 (suppl 1): S77–84. Relman DA, Falkow S. A molecular perspective of microbial pathogenicity. In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases, 3rd edn. New York: Churchill Livingstone, 1990: 26.
THE LANCET • Vol 360 • December 21/28, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
CORRESPONDENCE
4
5
Benhamou Y, Bochet M, Di Martino V, et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. Hepatology 1999; 30: 1054–58. Benhamou Y, Di Martino V, Bochet M, et al. Factors affecting liver fibrosis in human immunodeficiency virus- and hepatitis C virus-coinfected patients: impact of protease inhibitor therapy. Hepatology 2001; 34: 283–87.
Author’s reply Sir—The definition of hepatitis C virus (HCV) as an opportunistic pathogen in HIV-infected individuals has been used by the US Public Health Service and the Infectious Diseases Society of America.1 Sandro Vento’s citation of D Relman and S Falkow2 refers to the conventional definition of opportunistic pathogens as organisms that “have limited growth opportunities outside of their restricted niche in an unimpaired individual”. However, Relman and Falkow go on to state that “virtually any microorganism with a capacity for sustained multiplication in humans can cause disease more readily in individuals with underlying chronic disease or who are otherwise compromised”.2 HCV should be classified as an opportunistic pathogen in individuals with HIV infection, because they have an increased incidence of chronic infection after acute exposure compared with individuals without HIV infection.3 Similarly, among individuals with chronic HCV infection, the natural history of hepatic fibrosis progression is accelerated in those who are also infected with HIV.4 Mycobacterium tuberculosis is an additional example of an opportunistic pathogen that can cause disease in immunocompetent individuals but with altered incidence and natural history in HIV-infected individuals. Therefore, the definition of an opportunistic pathogen in HIVinfected individuals should be extended to include those pathogens that have an increased incidence of infection and an altered natural history in immunocompromised hosts. Abstinence from substance misuse, including alcohol, is an important consideration in the management of HCV-infected individuals, irrespective of whether or not they are also infected with HIV. Although avoidance of alcohol and control of HIV replication with antiretroviral agents may slow the rate of hepatic fibrosis progression, there are no prospective data to lend support to
this hypothesis. Furthermore, even in the absence of alcohol use and HIV infection, hepatitis C can lead to cirrhosis, liver failure, and hepatocellular carcinoma. Interferon with or without ribavirin can eradicate HCV in some chronically infected individuals, including those coinfected with HIV. Only by extending the use of these agents to special populations, including HIV/HCV coinfected individuals, will a greater number of patients benefit from HCV therapy. The need to provide HCV treatment to people coinfected with HIV was addressed in the National Institutes of Health Consensus Development Conference Panel, which concluded that “treatment of HCV infection in patients with HIV is recommended on a case-by-case basis”.5 Andrew Talal Center for the Study of Hepatitis C, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA (e-mail: [email protected]) 1
2
3
4
5
Guidelines for preventing opportunistic infections among HIV-infected persons— 2002 recommendations of the US Public Health Service and the Infectious Diseases Society of America. Available at http://www.cdc.gov/mmwr (accessed Sept 28, 2002). Relman DA, Falkow S. A molecular perspective of microbial pathogenicity. In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases, 3rd edn. New York: Churchill Livingston, 1990: 26. Thomas DL, Astemborski J, Rai RM, et al. The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA 2000; 284: 450–56. Sulkowski MS, Mast EE, Seeff LB, Thomas DL. Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus. Clin Infect Dis 2000; 30 (suppl 1): S77–84. National Institutes of Health consensus development conference statement. Management of hepatitis C: 2002. June 10–12, 2002. Available at http://consensus.nih.gov/cons/116/0912021 16cdc_statement.htm (accessed Oct 4, 2002).
Country France Germany Netherlands Spain UK Total
W135 meningococcal carriage in Hajj pilgrims Sir—Annelies Wilder-Smith and colleagues (Aug 24, p 644)1,2 report a 15% rate of acquisition of W135 Neisseria meningitidis among Singaporean pilgrims, all of whom were vaccinated with quadrivalent vaccine, during the Hajj in 2001. They argue that eradication of carriage among returning Hajj pilgrims might be needed to prevent meningococcal disease in their contacts. Wilder-Smith’s results contrast with those from a study among American Hajj pilgrims also in 2001, in whom the rate of acquisition of W135 carriage was only 0·8%.3 Since all pilgrims were vaccinated with quadrivalent vaccine, these studies cannot be used to estimate the effect of vaccination on carriage. The discrepancy in results suggests that variables such as mixing patterns, herdimmunity, and type of accommodation during the Hajj could be stronger determinants of the risk of acquisition of carriage. After Hajj 2001, however, for 94% (16) of cases in contacts of pilgrims in the UK, none of the pilgrims had received quadrivalent vaccine, whereas about half of all pilgrims had.4 This observation is consistent with quadrivalent vaccine providing some individual protection against carriage. The prevalence of N meningitidis carriage among European Hajj pilgrims has never been documented. Nevertheless, to guide interventions to prevent meningococcal disease, occurrence of invasive disease is ultimately more informative. To monitor this rate, the Invasive Bacterial Infections Surveillance Network in the European Union (EU-IBIS) established a sentinel rapid reporting system for cases of invasive disease caused by the outbreak strain (W135: 2a:P1-2,5 or phenotypically compatible strains) in six EUmember states.5 From week 36 in 2000 to week 30 in 2002 inclusive, 159 cases were reported, of which 25 (16%) were fatal. Seven of
Cases in pilgrims
Cases in contacts of pilgrims
Cases for which no association with Hajj was identified
2001
2002
2001
2002
2001
2002
0 0 0 0 6 6
0 0 0 0 0 0
3 1 2 0 19 25
0 0 0 0 2 2
11 5 1 16 34 34
12 3 1 2 18 18
Number of cases of meningococcal disease caused by N meningitidis W135 Zu:P1,2,5 or strains phenotypically compatible in equivalent periods in 2001 and 2002 (week 1–23 inclusive after the Hajj—ie, weeks 9–31 in 2001 and 8–30 in 2002)
THE LANCET • Vol 360 • December 21/28, 2002 • www.thelancet.com
2089
For personal use. Only reproduce with permission from The Lancet Publishing Group.
response (>40%) and of long-term disease-free survival (>10%, with follow-up >7 years). Moreover, after possible recurrence, the tumour should be retyped for TP53 status and, if mutated, the patient could be treated with paclitaxel. Such an approach to chemotherapy of ovarian carcinoma could allow delivery of optimum doses of the most effective single agent, avoiding the toxic effects expected by combination therapy. *Silvana Pilotti, Maria Oggionni, Silvia Böhm, Marco A Pierotti, Franco Zunino *Departments of Pathology, Experimental Oncology, and Preventive Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via G Venezian, 1-20133, Milan, Italy (e-mail: [email protected]) 1
2
3
4
5
The International Collaborative Ovarian Neoplasm (ICON) Group. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet 2002, 360: 505–15. Lavarino C, Pilotti S, Oggionni M, et al. P53 gene status and response to platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma. J Clin Oncol 2000; 18: 3936–45. Righetti SC, Della Torre G, Pilotti S, et al. A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma. Cancer Res 1996; 56: 689–93. Johnstone RW, Ruefli AA, Lowe SW. Apoptosis: a link between cancer genetics and chemotherapy. Cell 2002; 108: 153–64. Bohm S, Oriana S, Spatti G, et al. Dose intensification of platinum compounds with glutathione protection as induction chemotherapy for advanced ovarian carcinoma. Oncology 1999; 57: 115–20.
Authors’ reply Sir—We do not agree with the suggestions by Robert Ozols and colleagues that the results of GOG111 and OV10 are more believable than ours because these trials were done in a well defined population. ICON3 was a large randomised trial with simple outcome measures done in a population of women who are generally treated with chemotherapy for ovarian cancer. The suggestion by Ozols that the dose of carboplatin could explain our results is implausible, because the same carboplatin regimens were used in the control arm and the test arm; the test arm differed only by addition of paclitaxel to standard platinumbased chemotherapy. Furthermore, although we do not favour making direct comparisons of survival between trials, it should be noted that patients in both the control and
2088
research arms in ICON3 had very good outcome by any standard (median survival 36 months). The fact that ICON3 was large allowed us to do exploratory analyses by stage, residual bulk, histological type, differentiation, and age. This ability should be seen as the strength of a large trial rather than as a weakness, as suggested by Ozols. Both Earl and Ozols offer some suggestions to explain our results. In a systematic review1 of all relevant trials, these and other explanations have been considered to see whether they explain the clear conflict between positive (GOG111, OV10) and negative (GOG132 and ICON3) trials. In this review, trials were grouped by similarity of research regimens, similarity of control regimens, type of patients enrolled, and extent of crossover before progression. The results clearly showed that the broad entry criteria in ICON3 were not the reason for the discrepant results and, in particular, that considering only patients with bulky residual disease did not explain the conflicting results. Further, the suggestion that early use of other therapies in some trials may explain the results does not hold. Of the four explanations looked at, the only one that accorded with the results was the control regimen used. In particular, the two positive trials used the regimen of cyclophosphamide (750 mg/m2) and cisplatin (75 mg/m2) for their control arm. The review also examined external evidence, which lends support to this explanation.2 We should emphasise that ICON3 was not done or published to deny patients treatment or to claim that any other trials “got it wrong”. In our opinion, to present and discuss conflicting and complex data is important, however difficult that might be, so that patients and physicians can make informed choices about the true benefits of these chemotherapy regimens and, as Pilotti and colleagues point out, to motivate further research to improve outcomes for patients with ovarian cancer.
cisplatin chemotherapy of ovarian carcinoma: a meta-analysis. J Clin Oncol 1991; 9: 1668–74.
Hepatitis C virus in people with HIV infection Sir—In his Commentary, Andrew Talal (Aug 24, p 584) 1 defines hepatitis C virus (HCV) as an “opportunistic infection” when it occurs in individuals already infected with HIV. Although not new—M Sulkowski and colleagues2 use the same term—this definition is incorrect. An infection can be defined as opportunistic only when it causes no pathology in immunocompetent individuals and provokes serious organ damage in immunosuppressed patients, or when, as D Relman and S Falkow3 describe, “disease is a rare consequence of the host-microbe encounter”. These criteria clearly do not apply to HCV infection. Talal fails to account for two important issues. The first is the role of alcohol in progression of HCV infection in HIV-coinfected patients. This issue is important because many patients with HCV and HIV infection are injecting drug users who also misuse alcohol. Indeed, Benhamou and co-workers4 found that alcohol was an important factor in progression of hepatitis C to cirrhosis in HIV-coinfected patients. Secondly, the observation by Benhamou and colleagues5 that progression to cirrhosis is increased in patients with low CD4 cell-counts, implies that antiretroviral therapy per se can substantially slow such progression.5 Talal makes no mention of successful HIV treatment combined with reduction of alcohol intake to control progression of HCV-induced liver damage. This approach should be considered before rushing to use interferon and ribavirin, which is a combination therapy that has side-effects, potentially harmful interactions with antiretroviral drugs, and a still unsatisfying success rate. Sandro Vento Section of Infectious Diseases, Department of Pathology, University of Verona, 37138 Verona, Italy (e-mail: [email protected])
*Mahesh Parmar, Peter Harper, Nicoletta Colombo, Valter Torri, David Guthrie, on behalf of the ICON3 collaborators
1
MRC Clinical Trials Unit, London NWI 2DA, UK (e-mail: [email protected])
2
1
2
Sandercock J, Parmar MKB, Torri V, Qian W. Firstline treatment for advanced ovarian cancer: paclitaxel, platinum and the evidence. Br J Cancer 2002; 87: 815–24. Ovarian Cancer Meta-analysis Project. Cyclophosphamide plus cisplatin versus cyclophosphamide, doxorubicin and
3
Talal A. Opportunistic infections in HIVinfected individuals: hepatitis C virus. Lancet 2002; 360: 584–86. Sulkowski MS, Mast EE, Seeff LB, Thomas DL. Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus. Clin Infect Dis 2000; 30 (suppl 1): S77–84. Relman DA, Falkow S. A molecular perspective of microbial pathogenicity. In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases, 3rd edn. New York: Churchill Livingstone, 1990: 26.
THE LANCET • Vol 360 • December 21/28, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
CORRESPONDENCE
4
5
Benhamou Y, Bochet M, Di Martino V, et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. Hepatology 1999; 30: 1054–58. Benhamou Y, Di Martino V, Bochet M, et al. Factors affecting liver fibrosis in human immunodeficiency virus- and hepatitis C virus-coinfected patients: impact of protease inhibitor therapy. Hepatology 2001; 34: 283–87.
Author’s reply Sir—The definition of hepatitis C virus (HCV) as an opportunistic pathogen in HIV-infected individuals has been used by the US Public Health Service and the Infectious Diseases Society of America.1 Sandro Vento’s citation of D Relman and S Falkow2 refers to the conventional definition of opportunistic pathogens as organisms that “have limited growth opportunities outside of their restricted niche in an unimpaired individual”. However, Relman and Falkow go on to state that “virtually any microorganism with a capacity for sustained multiplication in humans can cause disease more readily in individuals with underlying chronic disease or who are otherwise compromised”.2 HCV should be classified as an opportunistic pathogen in individuals with HIV infection, because they have an increased incidence of chronic infection after acute exposure compared with individuals without HIV infection.3 Similarly, among individuals with chronic HCV infection, the natural history of hepatic fibrosis progression is accelerated in those who are also infected with HIV.4 Mycobacterium tuberculosis is an additional example of an opportunistic pathogen that can cause disease in immunocompetent individuals but with altered incidence and natural history in HIV-infected individuals. Therefore, the definition of an opportunistic pathogen in HIVinfected individuals should be extended to include those pathogens that have an increased incidence of infection and an altered natural history in immunocompromised hosts. Abstinence from substance misuse, including alcohol, is an important consideration in the management of HCV-infected individuals, irrespective of whether or not they are also infected with HIV. Although avoidance of alcohol and control of HIV replication with antiretroviral agents may slow the rate of hepatic fibrosis progression, there are no prospective data to lend support to
this hypothesis. Furthermore, even in the absence of alcohol use and HIV infection, hepatitis C can lead to cirrhosis, liver failure, and hepatocellular carcinoma. Interferon with or without ribavirin can eradicate HCV in some chronically infected individuals, including those coinfected with HIV. Only by extending the use of these agents to special populations, including HIV/HCV coinfected individuals, will a greater number of patients benefit from HCV therapy. The need to provide HCV treatment to people coinfected with HIV was addressed in the National Institutes of Health Consensus Development Conference Panel, which concluded that “treatment of HCV infection in patients with HIV is recommended on a case-by-case basis”.5 Andrew Talal Center for the Study of Hepatitis C, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA (e-mail: [email protected]) 1
2
3
4
5
Guidelines for preventing opportunistic infections among HIV-infected persons— 2002 recommendations of the US Public Health Service and the Infectious Diseases Society of America. Available at http://www.cdc.gov/mmwr (accessed Sept 28, 2002). Relman DA, Falkow S. A molecular perspective of microbial pathogenicity. In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases, 3rd edn. New York: Churchill Livingston, 1990: 26. Thomas DL, Astemborski J, Rai RM, et al. The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA 2000; 284: 450–56. Sulkowski MS, Mast EE, Seeff LB, Thomas DL. Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus. Clin Infect Dis 2000; 30 (suppl 1): S77–84. National Institutes of Health consensus development conference statement. Management of hepatitis C: 2002. June 10–12, 2002. Available at http://consensus.nih.gov/cons/116/0912021 16cdc_statement.htm (accessed Oct 4, 2002).
Country France Germany Netherlands Spain UK Total
W135 meningococcal carriage in Hajj pilgrims Sir—Annelies Wilder-Smith and colleagues (Aug 24, p 644)1,2 report a 15% rate of acquisition of W135 Neisseria meningitidis among Singaporean pilgrims, all of whom were vaccinated with quadrivalent vaccine, during the Hajj in 2001. They argue that eradication of carriage among returning Hajj pilgrims might be needed to prevent meningococcal disease in their contacts. Wilder-Smith’s results contrast with those from a study among American Hajj pilgrims also in 2001, in whom the rate of acquisition of W135 carriage was only 0·8%.3 Since all pilgrims were vaccinated with quadrivalent vaccine, these studies cannot be used to estimate the effect of vaccination on carriage. The discrepancy in results suggests that variables such as mixing patterns, herdimmunity, and type of accommodation during the Hajj could be stronger determinants of the risk of acquisition of carriage. After Hajj 2001, however, for 94% (16) of cases in contacts of pilgrims in the UK, none of the pilgrims had received quadrivalent vaccine, whereas about half of all pilgrims had.4 This observation is consistent with quadrivalent vaccine providing some individual protection against carriage. The prevalence of N meningitidis carriage among European Hajj pilgrims has never been documented. Nevertheless, to guide interventions to prevent meningococcal disease, occurrence of invasive disease is ultimately more informative. To monitor this rate, the Invasive Bacterial Infections Surveillance Network in the European Union (EU-IBIS) established a sentinel rapid reporting system for cases of invasive disease caused by the outbreak strain (W135: 2a:P1-2,5 or phenotypically compatible strains) in six EUmember states.5 From week 36 in 2000 to week 30 in 2002 inclusive, 159 cases were reported, of which 25 (16%) were fatal. Seven of
Cases in pilgrims
Cases in contacts of pilgrims
Cases for which no association with Hajj was identified
2001
2002
2001
2002
2001
2002
0 0 0 0 6 6
0 0 0 0 0 0
3 1 2 0 19 25
0 0 0 0 2 2
11 5 1 16 34 34
12 3 1 2 18 18
Number of cases of meningococcal disease caused by N meningitidis W135 Zu:P1,2,5 or strains phenotypically compatible in equivalent periods in 2001 and 2002 (week 1–23 inclusive after the Hajj—ie, weeks 9–31 in 2001 and 8–30 in 2002)
THE LANCET • Vol 360 • December 21/28, 2002 • www.thelancet.com
2089
For personal use. Only reproduce with permission from The Lancet Publishing Group.