Effectiveness of antibiotics in preventing meningococcal disease after a case: systematic review
http://www.100md.com
《英国医生杂志》
1 Communicable Disease Surveillance Centre South West, Gloucester GL10 3RF, 2 Statens Serum Institut, Copenhagen, Denmark 2300, 3 Communicable Disease Surveillance Centre, Cardiff, Wales CF4 3QX, 4 Landesuntersuchungsanstalt für das Gesundheits und Veterin?rwesen, Dresden, Germany 01099, 5 National Reference Centre for Meningococci, Graz, Austria A-8010, 6 Public Health Laboratory Service Statistics Unit, Colindale, London NW9 5EQ
Correspondence to: J Stuart james.stuart@hpa.org.uk
Abstract
The search identified 2606 papers. After reviewing titles and abstracts we retrieved 102 as potentially relevant. Of these, five studies met the criteria for this review. Of the excluded reports, many were descriptive accounts of outbreaks and case reports, some addressed a different set of questions or did not evaluate an intervention, and others did not report the outcomes of primary interest or had no comparison group. We did not identify any studies of day care and nursery schools that met our criteria.
Evidence of benefit from chemoprophylaxis to household contacts
Five studies satisfied our inclusion criteria, four retrospective cohort studies and one small trial.5 12-15 In total they involved 1249 sporadic cases of meningococcal disease and about 4271 household contacts. The only experimental study was a small randomised trial within a larger seroepidemiological survey.12 Fifty four contacts from 11 affected households were randomised to receive rifampicin (35) or no treatment (19). No subsequent cases occurred in either group after nine months (table 1).
Table 1 Effectiveness of antibiotics to contacts after case of meningococcal disease: study characteristics
The largest and most frequently cited study used enhanced surveillance of a case series in 27 US states between 1973 and 1974.5 This paper partly duplicated earlier findings.16 They found an attack rate of 4.2/1000 among untreated household contacts and no cases among treated contacts (table 2). This difference suggests that chemoprophylaxis is effective (relative risk 0.15, 95% confidence interval 0.01 to 2.79) but not significant.
Table 2 Estimate of effect of chemoprophylaxis given to household contacts after sporadic case of meningococcal disease
In a survey of meningococcal disease in the Netherlands from April 1989-May 1990,14 a secondary objective was to assess the attack rate among household contacts and document the uptake of chemoprophylaxis. Although it was not official policy to give chemoprophylaxis in the Netherlands during the study period, 55% (627 people from 220 families) of close contacts had received antibiotics. There were 502 primary cases reported during the study period. Information was available on 1130 household contacts in 75% (378) of these cases, and on antibiotics for 98% (1102) of these contacts. In the 30 day period after occurrence of the index case, there were four subsequent cases among 826 contacts that did not receive adequate chemoprophylaxis (including two in people who received penicillin) and no cases among 276 who had "optimal" treatment (0.33, 0.02 to 6.14, table 2).
In a study to evaluate the efficiency of the implementation of prophylactic measures in Denmark,15 there were no cases among 724 treated contacts and two among 72 who were not treated (0.02, 0.00 to 0.42, table 2). The two subsequent cases were in friends of the index patients who had slept in the same room as their respective index case. No further information was available on 56% of cases (table 1).
Kristiansen's study, among the 165 000 inhabitants of Telemark in Norway, examined whether a policy of targeted prophylaxis with rifampicin for contacts carrying the meningococcal strain that caused the disease could limit the spread of infection more efficiently than treatment with penicillin alone to household members aged under 15 years.13 No subsequent cases occurred among 441 potential contacts screened and treated with rifampicin compared with 15 (11 confirmed) cases in 1984-87, when only penicillin was given. Although this study suggests benefit from the targeted intervention, we could not measure risk reduction as the number of contacts was not available for the earlier time period. The follow up period was much longer and the contact definitions were much broader than the definitions used for our review.
Summary effect estimates for chemoprophylaxis versus no treatment
Three studies, in the United States, Denmark, and the Netherlands, had sufficiently similar characteristics (clinical homogeneity) for inclusion in the meta-analysis.5 14 15 We did not include Kaiser's study12 as there were no events in treatment or intervention group.
The summary risk ratio was 0.11 (0.02 to 0.58; figure). This implies that chemoprophylaxis given to household contacts after a case of meningococcal disease reduces the risk of subsequent cases by 89%. Results of tests for heterogeneity were not significant (P = 0.39). The pooled absolute risk reduction was 46/10 000 (9/10 000 to 83/10 000), and the number needed to treat to prevent a case was estimated as 218 (121 to 1135).
Effect of chemoprophylaxis given to household contacts after a case of meningococcal disease on risk of subsequent cases: pooled risk ratio
Evidence for use of chemoprophylaxis in index patients before discharge from hospital
We found no studies comparing index patients given chemoprophylaxis with those who were not. Four studies assessed persistent meningogcoccal carriage on discharge from hospital in patients who had not received chemoprophylaxis. Alvez et al showed that three of 48 children (aged 3 months to 13 years) who were treated with 300 000 units/kg/day of penicillin G sodium intravenously for at least 10 days were carriers of Neisseria meningitidis on discharge.17 In the study of Abramson and Spika meningococci were cultured from the upper respiratory tract in one of 14 patients discharged after completion of intravenous therapy, initially with ampicillin or chloramphenicol then benzyl penicillin.18 Four patients had positive cultures one week after the end of treatment. The household contacts of the patients, but not the patients themselves, had received chemoprophylaxis with rifampicin. Barroso found two of 51 patients had positive nasopharyngeal swabs after the end of their treatment,19 though the exact timing of the swabs in relation to hospital discharge (eight hours after the end of treatment to six days after discharge) is not clear. The patients had been treated with ampicillin, penicillin, or chloramphenicol. Weis found no carriers among 47 patients on discharge.20 Although this study did not specify the antibiotic treatment used, benzyl penicillin was then the standard treatment for meningococcal disease in Denmark (S Samuelsson, personal communication).
The four studies were included in meta-analysis. Results of tests for heterogeneity were not significant (P = 0.35). The pooled estimate from these studies was calculated as 0.03 (0.00 to 0.06, table 3).
Table 3 Estimated carriage rate on discharge from hospital in index patients not treated with chemoprophylaxis. Meta-analysis results
Discussion
We found that if household contacts of a patient with meningococcal disease are given prophylaxis with antibiotics that eradicate meningococcal carriage there are fewer subsequent cases. The reduction in risk is considerable. We estimate that about 200 household contacts need to be treated to prevent a subsequent case during the first month. This applies to a strategy of giving chemoprophylaxis to a network of household contacts but provides no evidence to support indiscriminate prescribing of antibiotic prophylaxis to people outside this group.
The main difficulty in interpreting the findings is that they are obtained from retrospective observational studies. Risk factors for meningococcal disease, such as young age, male sex, passive smoking, and lower socioeconomic status, are all potential confounding factors.21 22 None of the studies took account of these factors in their analysis. There is evidence that people of lower socioeconomic status are less likely to receive preventive interventions.23 If this were the case for meningococcal disease, these observational studies would overestimate the true benefit of treatment. On the other hand, adults have a lower baseline risk of disease and if children were more likely to get prophylaxis than adults this would underestimate the true effect. The studies gave no baseline comparisons of age distribution between treated and untreated groups. If efforts to achieve follow up had differed in some way between treated and untreated groups, this would only dilute the observed effect of treatment, unless the investigators had somehow applied different stringency of criteria (for instance, for case definitions) between groups. The risk to untreated household contacts is highest in the first week after the index case and declines rapidly thereafter.24 A one month period to measure risk reduction is therefore reasonable but does not assess whether chemoprophylaxis could prevent subsequent cases beyond this period.25
Previous studies have suggested that subsequent cases may be caused by reintroduction of the virulent strain to the household by the index patient.26 We estimate that about 3% of index patients treated with penicillin and who have not received chemoprophylaxis will still be carrying the virulent strain on discharge from hospital. As carriage may be suppressed but not eradicated by penicillin treatment so that carriage is less easily detected on completion of treatment,18 this figure is likely to underestimate the true carriage rate among index patients. Giving chemoprophylaxis to the index patient before discharge from hospital should also be supported, unless they have already been treated with an antibiotic such as ceftriaxone, which is known to eradicate carriage.
Studies to estimate the effect of chemoprophylaxis in day care settings are needed, and the current variation in policy across European countries is therefore not surprising. As clusters are unusual in this setting and as policies vary by country, a multinational study may be needed to provide evidence on benefit.
This is the first systematic review of evidence for control policies for meningococcal disease and supports giving a short course of antibiotics that eradicate carriage to household contacts and index patients. The consistency of the study findings, the size of the risk ratio, and the biological plausibility of this approach lend further weight to our conclusions. We believe that such a policy should be applied across Europe and other industrialised countries.
What is already known on this topic
A lack of evidence for strategies to control meningococcal disease has resulted in a variation in approach among countries in Europe
Most countries recommend a short course of rifampicin or ciprofloxacin for all household contacts but evidence to support this has previously been limited to one observational study
There are no uniform recommendations for giving chemoprophylaxis to the index patient or to contacts in childcare settings
What this study adds
Evidence from three studies supports the use of chemoprophylaxis to prevent further cases of meningococcal disease
The risk of further cases during the first month is reduced by 89%, and to prevent one case about 200 household contacts need to be treated
After treatment of disease with penicillin and without giving chemoprophylaxis, at least 3% of index patients will be carrying the virulent meningococcal strain on discharge from hospital
There are insufficient studies to estimate the effect of chemoprophylaxis in childcare settings
Julie Christmas and Potenza Atiogbe helped with the search strategy and database searches. Maria Santamaria reviewed the initial dataset. Matthias Egger gave advice on the methods and earlier drafts.
Contributors: JMS conceived the study. All authors except AC contributed to the design of the study, carried out searches, and extracted data. AC performed the meta-analyses. BP wrote the first draft. All authors were involved in the writing of the final draft. JMS is guarantor for this study.
Funding: During part of this study, SJMH and IC were funded by the European Programme for Intervention Epidemiology Training (EPIET), which is funded by the European Commission under the agreement numberSI2.74030 (99CVVF4-003-0). Two meetings of the working group were supported by Wyeth Lederle.
Ethical approval: Not required.
References
Begg N. Policies for public health management of meningococcal disease. J Epidemiol Community Health 1999;53: 516.
Samuelsson S. Surveillance and prevention of meningococcal disease in Denmark 1980-96. Odense: University of Southern Denmark, 1999: 30.
Cuevas LE, Hart CA. Chemoprophylaxis of bacterial meningitis. J Antimicrob Chemother 1993;31(suppl B): 79-91.
Band JD, Fraser DW, Ajello G, Hemophilus Influenzae Disease Study Group. Prevention of Hemophilus influenzae type b disease. JAMA 1984;251: 2381-6.
Meningococcal Disease Surveillance Group. Analysis of endemic meningococcal disease by serogroup and evaluation of chemoprophylaxis. J Infect Dis 1976;134: 201-4.
Yagupsky P, Ashkenaxi S, Block C. Rifampicin-resistant meningococci causing invasive disease and failure of chemoprophylaxis. Lancet 1993;341: 1152-3.
Allergic reactions to ciprofloxacin chemoprophylaxis. Commun Dis Rep CDR Wkly 1999;12;9: 95,98.
Hall AP, Thorpe JM, Seaton D. Case report of profound thrombocytopenia. J Antimicrob Chemother 1993;31: 451.
Pearson N, Gunnell DJ, Dunn C, Beswick T, Hill A, Ley B. Antibiotic prophylaxis for bacterial meningitis: overuse and uncertain efficacy. J Publ Hlth Med 1995;17: 455-8.
Strengthening Europe's defences against health threats: commission proposes European Centre for Disease Prevention and Control. Brussels: European Commission, 23 July 2003 (press release IP/03/1091). http://europa.eu.int/comm/health/ph_overview/strategy/ecdc/ecdc_en.htm (accessed 3 Aug 2003).
Bradburn MJ, Deeks JJ, Altman DG. sbe24: metan-an alternative meta-analysis command. Stata Technical Bulletin 1998;41: 4-15.
Kaiser AB, Hennekens CH, Saslaw MS, Hayes PS, Bennett JV. Seroepidemiology and chemoprophylaxis of disease due to sulfonamide-resistant Neisseria menigitidis in a civilian population. J Infect Dis 1974;130: 217-24.
Kristiansen BE, Tveten Y, Reiten J, Knapskog AB. Preventing secondary cases of meningococcal disease by identifying and eradicating disease-causing strains in close contacts of patients. Scand J Infect Dis 1992;24: 165-73.
Scholten RJ, Bijlmer HA, Dankert J, Valkenburg HA. (In Dutch.) Ned Tijdschr Geneeskd 1993;137: 1505-8.
Samuelsson S, Hansen ET, Osler M, Jeune B. Prevention of secondary cases of meningococcal disease in Denmark. Epidemiol Infect 2000;124: 433-40.
Meningococcal Disease Surveillance Group. Meningococcal disease: secondary attack rate and chemoprophylaxis in the United States, 1974. JAMA 1976;235: 261-5.
Alvez F, Aguilera A, Garcia-Zabarte A, Castro-Gago MD. Effect of chemoprophylaxis on the meningococcal carrier state after systemic infection. Pediatr Infect Dis J 1991;10: 700.
Abramson JS, Spika JS. Persistence of Neisseria meningitidis in the upper respiratory tract after intravenous antibiotic therapy for systemic meningococcal disease. J Infect Dis 1985;151: 370-1.
Barroso D. Neisseria meningitidis nasopharynx colonization of diseased patients on presentation and on discharge. Trop Doct 1999;29: 108-9.
Weis N, Lind I. Pharyngeal carriage of Neisseria meningitidis before and after treatment of meningococcal disease. J Med Microbiol 1994;41: 339-42.
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.
Jones IR, Urwin G, Feldman RA, Banatvala N. Social deprivation and bacterial meningitis in North East Thames region: three year study using small statistics. BMJ 1997;314: 794-7.
Campbell SM, Hann M, Hacker J, Burns C, Oliver D, Thapar A, et al. Identifying predictors of high quality care in English general practice: observational study. BMJ 2001;323: 784-7.
De Wals P, Hertoghe L, Borlee-Grimee I, De Maeyer-Cleempoel S, Reginster-Haneuse G, Dachy A, et al. Meningococcal disease in Belgium. Secondary attack rate among household, day-care nursery and pre-elementary school contacts. J Infect 1981;3(suppl 1): 53-61.
Stuart JM, Cartwright KAV, Robinson PM, Noah ND. Does eradication of meningococcal carriage in household contacts prevent secondary cases of meningococcal disease? BMJ 1989;298: 569.
Cooke RPD, Riordan T, Jones DM, Painter MJ. Secondary cases of meningococcal infection among close family and household contacts in England and Wales, 1984-7. BMJ 1989;298: 555-8.(Bernadette Purcell, speci)
Correspondence to: J Stuart james.stuart@hpa.org.uk
Abstract
The search identified 2606 papers. After reviewing titles and abstracts we retrieved 102 as potentially relevant. Of these, five studies met the criteria for this review. Of the excluded reports, many were descriptive accounts of outbreaks and case reports, some addressed a different set of questions or did not evaluate an intervention, and others did not report the outcomes of primary interest or had no comparison group. We did not identify any studies of day care and nursery schools that met our criteria.
Evidence of benefit from chemoprophylaxis to household contacts
Five studies satisfied our inclusion criteria, four retrospective cohort studies and one small trial.5 12-15 In total they involved 1249 sporadic cases of meningococcal disease and about 4271 household contacts. The only experimental study was a small randomised trial within a larger seroepidemiological survey.12 Fifty four contacts from 11 affected households were randomised to receive rifampicin (35) or no treatment (19). No subsequent cases occurred in either group after nine months (table 1).
Table 1 Effectiveness of antibiotics to contacts after case of meningococcal disease: study characteristics
The largest and most frequently cited study used enhanced surveillance of a case series in 27 US states between 1973 and 1974.5 This paper partly duplicated earlier findings.16 They found an attack rate of 4.2/1000 among untreated household contacts and no cases among treated contacts (table 2). This difference suggests that chemoprophylaxis is effective (relative risk 0.15, 95% confidence interval 0.01 to 2.79) but not significant.
Table 2 Estimate of effect of chemoprophylaxis given to household contacts after sporadic case of meningococcal disease
In a survey of meningococcal disease in the Netherlands from April 1989-May 1990,14 a secondary objective was to assess the attack rate among household contacts and document the uptake of chemoprophylaxis. Although it was not official policy to give chemoprophylaxis in the Netherlands during the study period, 55% (627 people from 220 families) of close contacts had received antibiotics. There were 502 primary cases reported during the study period. Information was available on 1130 household contacts in 75% (378) of these cases, and on antibiotics for 98% (1102) of these contacts. In the 30 day period after occurrence of the index case, there were four subsequent cases among 826 contacts that did not receive adequate chemoprophylaxis (including two in people who received penicillin) and no cases among 276 who had "optimal" treatment (0.33, 0.02 to 6.14, table 2).
In a study to evaluate the efficiency of the implementation of prophylactic measures in Denmark,15 there were no cases among 724 treated contacts and two among 72 who were not treated (0.02, 0.00 to 0.42, table 2). The two subsequent cases were in friends of the index patients who had slept in the same room as their respective index case. No further information was available on 56% of cases (table 1).
Kristiansen's study, among the 165 000 inhabitants of Telemark in Norway, examined whether a policy of targeted prophylaxis with rifampicin for contacts carrying the meningococcal strain that caused the disease could limit the spread of infection more efficiently than treatment with penicillin alone to household members aged under 15 years.13 No subsequent cases occurred among 441 potential contacts screened and treated with rifampicin compared with 15 (11 confirmed) cases in 1984-87, when only penicillin was given. Although this study suggests benefit from the targeted intervention, we could not measure risk reduction as the number of contacts was not available for the earlier time period. The follow up period was much longer and the contact definitions were much broader than the definitions used for our review.
Summary effect estimates for chemoprophylaxis versus no treatment
Three studies, in the United States, Denmark, and the Netherlands, had sufficiently similar characteristics (clinical homogeneity) for inclusion in the meta-analysis.5 14 15 We did not include Kaiser's study12 as there were no events in treatment or intervention group.
The summary risk ratio was 0.11 (0.02 to 0.58; figure). This implies that chemoprophylaxis given to household contacts after a case of meningococcal disease reduces the risk of subsequent cases by 89%. Results of tests for heterogeneity were not significant (P = 0.39). The pooled absolute risk reduction was 46/10 000 (9/10 000 to 83/10 000), and the number needed to treat to prevent a case was estimated as 218 (121 to 1135).
Effect of chemoprophylaxis given to household contacts after a case of meningococcal disease on risk of subsequent cases: pooled risk ratio
Evidence for use of chemoprophylaxis in index patients before discharge from hospital
We found no studies comparing index patients given chemoprophylaxis with those who were not. Four studies assessed persistent meningogcoccal carriage on discharge from hospital in patients who had not received chemoprophylaxis. Alvez et al showed that three of 48 children (aged 3 months to 13 years) who were treated with 300 000 units/kg/day of penicillin G sodium intravenously for at least 10 days were carriers of Neisseria meningitidis on discharge.17 In the study of Abramson and Spika meningococci were cultured from the upper respiratory tract in one of 14 patients discharged after completion of intravenous therapy, initially with ampicillin or chloramphenicol then benzyl penicillin.18 Four patients had positive cultures one week after the end of treatment. The household contacts of the patients, but not the patients themselves, had received chemoprophylaxis with rifampicin. Barroso found two of 51 patients had positive nasopharyngeal swabs after the end of their treatment,19 though the exact timing of the swabs in relation to hospital discharge (eight hours after the end of treatment to six days after discharge) is not clear. The patients had been treated with ampicillin, penicillin, or chloramphenicol. Weis found no carriers among 47 patients on discharge.20 Although this study did not specify the antibiotic treatment used, benzyl penicillin was then the standard treatment for meningococcal disease in Denmark (S Samuelsson, personal communication).
The four studies were included in meta-analysis. Results of tests for heterogeneity were not significant (P = 0.35). The pooled estimate from these studies was calculated as 0.03 (0.00 to 0.06, table 3).
Table 3 Estimated carriage rate on discharge from hospital in index patients not treated with chemoprophylaxis. Meta-analysis results
Discussion
We found that if household contacts of a patient with meningococcal disease are given prophylaxis with antibiotics that eradicate meningococcal carriage there are fewer subsequent cases. The reduction in risk is considerable. We estimate that about 200 household contacts need to be treated to prevent a subsequent case during the first month. This applies to a strategy of giving chemoprophylaxis to a network of household contacts but provides no evidence to support indiscriminate prescribing of antibiotic prophylaxis to people outside this group.
The main difficulty in interpreting the findings is that they are obtained from retrospective observational studies. Risk factors for meningococcal disease, such as young age, male sex, passive smoking, and lower socioeconomic status, are all potential confounding factors.21 22 None of the studies took account of these factors in their analysis. There is evidence that people of lower socioeconomic status are less likely to receive preventive interventions.23 If this were the case for meningococcal disease, these observational studies would overestimate the true benefit of treatment. On the other hand, adults have a lower baseline risk of disease and if children were more likely to get prophylaxis than adults this would underestimate the true effect. The studies gave no baseline comparisons of age distribution between treated and untreated groups. If efforts to achieve follow up had differed in some way between treated and untreated groups, this would only dilute the observed effect of treatment, unless the investigators had somehow applied different stringency of criteria (for instance, for case definitions) between groups. The risk to untreated household contacts is highest in the first week after the index case and declines rapidly thereafter.24 A one month period to measure risk reduction is therefore reasonable but does not assess whether chemoprophylaxis could prevent subsequent cases beyond this period.25
Previous studies have suggested that subsequent cases may be caused by reintroduction of the virulent strain to the household by the index patient.26 We estimate that about 3% of index patients treated with penicillin and who have not received chemoprophylaxis will still be carrying the virulent strain on discharge from hospital. As carriage may be suppressed but not eradicated by penicillin treatment so that carriage is less easily detected on completion of treatment,18 this figure is likely to underestimate the true carriage rate among index patients. Giving chemoprophylaxis to the index patient before discharge from hospital should also be supported, unless they have already been treated with an antibiotic such as ceftriaxone, which is known to eradicate carriage.
Studies to estimate the effect of chemoprophylaxis in day care settings are needed, and the current variation in policy across European countries is therefore not surprising. As clusters are unusual in this setting and as policies vary by country, a multinational study may be needed to provide evidence on benefit.
This is the first systematic review of evidence for control policies for meningococcal disease and supports giving a short course of antibiotics that eradicate carriage to household contacts and index patients. The consistency of the study findings, the size of the risk ratio, and the biological plausibility of this approach lend further weight to our conclusions. We believe that such a policy should be applied across Europe and other industrialised countries.
What is already known on this topic
A lack of evidence for strategies to control meningococcal disease has resulted in a variation in approach among countries in Europe
Most countries recommend a short course of rifampicin or ciprofloxacin for all household contacts but evidence to support this has previously been limited to one observational study
There are no uniform recommendations for giving chemoprophylaxis to the index patient or to contacts in childcare settings
What this study adds
Evidence from three studies supports the use of chemoprophylaxis to prevent further cases of meningococcal disease
The risk of further cases during the first month is reduced by 89%, and to prevent one case about 200 household contacts need to be treated
After treatment of disease with penicillin and without giving chemoprophylaxis, at least 3% of index patients will be carrying the virulent meningococcal strain on discharge from hospital
There are insufficient studies to estimate the effect of chemoprophylaxis in childcare settings
Julie Christmas and Potenza Atiogbe helped with the search strategy and database searches. Maria Santamaria reviewed the initial dataset. Matthias Egger gave advice on the methods and earlier drafts.
Contributors: JMS conceived the study. All authors except AC contributed to the design of the study, carried out searches, and extracted data. AC performed the meta-analyses. BP wrote the first draft. All authors were involved in the writing of the final draft. JMS is guarantor for this study.
Funding: During part of this study, SJMH and IC were funded by the European Programme for Intervention Epidemiology Training (EPIET), which is funded by the European Commission under the agreement numberSI2.74030 (99CVVF4-003-0). Two meetings of the working group were supported by Wyeth Lederle.
Ethical approval: Not required.
References
Begg N. Policies for public health management of meningococcal disease. J Epidemiol Community Health 1999;53: 516.
Samuelsson S. Surveillance and prevention of meningococcal disease in Denmark 1980-96. Odense: University of Southern Denmark, 1999: 30.
Cuevas LE, Hart CA. Chemoprophylaxis of bacterial meningitis. J Antimicrob Chemother 1993;31(suppl B): 79-91.
Band JD, Fraser DW, Ajello G, Hemophilus Influenzae Disease Study Group. Prevention of Hemophilus influenzae type b disease. JAMA 1984;251: 2381-6.
Meningococcal Disease Surveillance Group. Analysis of endemic meningococcal disease by serogroup and evaluation of chemoprophylaxis. J Infect Dis 1976;134: 201-4.
Yagupsky P, Ashkenaxi S, Block C. Rifampicin-resistant meningococci causing invasive disease and failure of chemoprophylaxis. Lancet 1993;341: 1152-3.
Allergic reactions to ciprofloxacin chemoprophylaxis. Commun Dis Rep CDR Wkly 1999;12;9: 95,98.
Hall AP, Thorpe JM, Seaton D. Case report of profound thrombocytopenia. J Antimicrob Chemother 1993;31: 451.
Pearson N, Gunnell DJ, Dunn C, Beswick T, Hill A, Ley B. Antibiotic prophylaxis for bacterial meningitis: overuse and uncertain efficacy. J Publ Hlth Med 1995;17: 455-8.
Strengthening Europe's defences against health threats: commission proposes European Centre for Disease Prevention and Control. Brussels: European Commission, 23 July 2003 (press release IP/03/1091). http://europa.eu.int/comm/health/ph_overview/strategy/ecdc/ecdc_en.htm (accessed 3 Aug 2003).
Bradburn MJ, Deeks JJ, Altman DG. sbe24: metan-an alternative meta-analysis command. Stata Technical Bulletin 1998;41: 4-15.
Kaiser AB, Hennekens CH, Saslaw MS, Hayes PS, Bennett JV. Seroepidemiology and chemoprophylaxis of disease due to sulfonamide-resistant Neisseria menigitidis in a civilian population. J Infect Dis 1974;130: 217-24.
Kristiansen BE, Tveten Y, Reiten J, Knapskog AB. Preventing secondary cases of meningococcal disease by identifying and eradicating disease-causing strains in close contacts of patients. Scand J Infect Dis 1992;24: 165-73.
Scholten RJ, Bijlmer HA, Dankert J, Valkenburg HA. (In Dutch.) Ned Tijdschr Geneeskd 1993;137: 1505-8.
Samuelsson S, Hansen ET, Osler M, Jeune B. Prevention of secondary cases of meningococcal disease in Denmark. Epidemiol Infect 2000;124: 433-40.
Meningococcal Disease Surveillance Group. Meningococcal disease: secondary attack rate and chemoprophylaxis in the United States, 1974. JAMA 1976;235: 261-5.
Alvez F, Aguilera A, Garcia-Zabarte A, Castro-Gago MD. Effect of chemoprophylaxis on the meningococcal carrier state after systemic infection. Pediatr Infect Dis J 1991;10: 700.
Abramson JS, Spika JS. Persistence of Neisseria meningitidis in the upper respiratory tract after intravenous antibiotic therapy for systemic meningococcal disease. J Infect Dis 1985;151: 370-1.
Barroso D. Neisseria meningitidis nasopharynx colonization of diseased patients on presentation and on discharge. Trop Doct 1999;29: 108-9.
Weis N, Lind I. Pharyngeal carriage of Neisseria meningitidis before and after treatment of meningococcal disease. J Med Microbiol 1994;41: 339-42.
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.
Jones IR, Urwin G, Feldman RA, Banatvala N. Social deprivation and bacterial meningitis in North East Thames region: three year study using small statistics. BMJ 1997;314: 794-7.
Campbell SM, Hann M, Hacker J, Burns C, Oliver D, Thapar A, et al. Identifying predictors of high quality care in English general practice: observational study. BMJ 2001;323: 784-7.
De Wals P, Hertoghe L, Borlee-Grimee I, De Maeyer-Cleempoel S, Reginster-Haneuse G, Dachy A, et al. Meningococcal disease in Belgium. Secondary attack rate among household, day-care nursery and pre-elementary school contacts. J Infect 1981;3(suppl 1): 53-61.
Stuart JM, Cartwright KAV, Robinson PM, Noah ND. Does eradication of meningococcal carriage in household contacts prevent secondary cases of meningococcal disease? BMJ 1989;298: 569.
Cooke RPD, Riordan T, Jones DM, Painter MJ. Secondary cases of meningococcal infection among close family and household contacts in England and Wales, 1984-7. BMJ 1989;298: 555-8.(Bernadette Purcell, speci)