Summary

These recommendations update information regarding the polysaccharide vaccine licensed in the United States for use against disease caused by Neisseria meningitidis serogroups A, C, Y, and W-135, as well as antimicrobial agents for chemoprophylaxis against meningococcal disease (superseding MMWR 1985;34:255-9). This report provides additional information regarding meningococcal vaccines and the addition of ciprofloxacin and ceftriaxone as acceptable alternatives to rifampin for chemoprophylaxis in selected populations.

INTRODUCTION

Neisseria meningitidis causes both endemic and epidemic disease, principally meningitis and meningococcemia (1). As a result of the control of Haemophilus influenzae type b infections, N. meningitidis has become the leading cause of bacterial meningitis in children and young adults in the United States, with an estimated 2,600 cases each year (2). The case-fatality rate is 13% for meningitic disease (defined as the isolation of N. meningitidis from cerebrospinal fluid) and 11.5% for persons who have N. meningitidis isolated from blood (2), despite therapy with antimicrobial agents (e.g., penicillin) to which U.S. strains remain clinically sensitive (3).

The incidence of meningococcal disease peaks in late winter to early spring. Attack rates are highest among children 3-12 months of age and then steadily decline among older age groups (Figure_1). Based on multistate surveillance conducted during 1989-1991, serogroup B organisms accounted for 46% of all cases and serogroup C for 45%; serogroups W-135 and Y and strains that could not be serotyped accounted for most of the remaining cases (2). Recent data indicate that the proportion of cases caused by serogroup Y strains is increasing (4). Serogroup A, which rarely causes disease in the United States, is the most common cause of epidemics in Africa and Asia. In the United States, localized community outbreaks of serogroup C disease and a statewide serogroup B epidemic have recently been reported (5,6).

Persons who have certain medical conditions are at increased risk for developing meningococcal infection. Meningococcal disease is particularly common among persons who have component deficiencies in the terminal common complement pathway (C3, C5-C9); many of these persons experience multiple episodes of infection (6). Asplenic persons also may be at increased risk for acquiring meningococcal disease with particularly severe infections (8). Persons who have other diseases associated with immunosuppression (e.g., human immunodeficiency virus {HIV} and Streptococcus pneumoniae) may be at higher risk for acquiring meningococcal disease and for disease caused by some other encapsulated bacteria. Evidence suggests that HIV-infected persons are not at substantially increased risk for epidemic serogroup A meningococcal disease (9); however, such patients may be at increased risk for sporadic meningococcal disease or disease caused by other meningococcal serogroups (10). Previously, military recruits had high rates of meningococcal disease, particularly serogroup C disease; however, since the initiation of routine vaccination of recruits with the bivalent A/C meningococcal vaccine in 1971, the high rates of meningococcal disease caused by those serogroups have decreased substantially and cases occur infrequently (11). Military recruits now routinely receive the quadrivalent A,C,Y, W-135 meningococcal vaccine.

MENINGOCOCCAL POLYSACCHARIDE VACCINE

The quadrivalent A,C,Y,W-135 vaccine (Menomune -A,C,Y,W-135, manufactured by Connaught Laboratories, Inc.) is the formulation currently available in the United States. The recommended dose of vaccine is a single 0.5-mL subcutaneous injection. Each vaccine dose consists of 50 ug each of the purified bacterial capsular polysaccharides. Menomune is available in single-dose, 10-dose, and 50-dose vials.

Vaccine Efficacy

The immunogenicity and clinical efficacy of the serogroups A and C meningococcal vaccines have been well established. The serogroup A polysaccharide induces antibody in some children as young as 3 months of age, although a response comparable with that among adults is not achieved until 4 or 5 years of age; the serogroup C component is poorly immunogenic in recipients who are less than 18-24 months of age (12,13). The serogroups A and C vaccines have demonstrated estimated clinical efficacies of 85%-100% in older children and adults and are useful in controlling epidemics (9,14-17). Serogroups Y and W-135 polysaccharides are safe and immunogenic in adults and in children greater than 2 years of age (18-21); although clinical protection has not been documented, vaccination with these polysaccharides induces bactericidal antibody. The antibody responses to each of the four polysaccharides in the quadrivalent vaccine are serogroup-specific and independent.

Duration of Efficacy

Measurable levels of antibodies against the group A and C polysaccharides decrease markedly during the first 3 years following a single dose of vaccine (13,22-25). This decrease in antibody occurs more rapidly in infants and young children than in adults. Similarly, although vaccine-induced clinical protection probably persists in schoolchildren and adults for at least 3 years, the efficacy of the group A vaccine in young children may decrease markedly with the passage of time: in a 3-year study, efficacy declined from greater than 90% to less than 10% among children who were less than 4 years of age at the time of vaccination, whereas among children who were greater than or equal to 4 years of age when vaccinated, efficacy was 67% 3 years later (26).

RECOMMENDATIONS FOR USE OF MENINGOCOCCAL VACCINE

Routine vaccination of civilians with the quadrivalent meningococcal polysaccharide vaccine is not recommended because of its relative ineffectiveness in children less than 2 years of age (among whom risk for endemic disease is highest) and its relatively short duration of protection. However, the polysaccharide meningococcal vaccine is useful for controlling serogroup C meningococcal outbreaks (27).

Indications for Use

In general, use of polysaccharide meningococcal vaccine should be restricted to persons greater than or equal to 2 years of age; however, children as young as 3 months of age may be vaccinated to elicit short-term protection against serogroup A meningococcal disease (two doses administered 3 months apart should be considered for children 3-18 months of age) (28).

Routine vaccination with the quadrivalent vaccine is recommended for certain high-risk groups, including persons who have terminal complement component deficiencies and those who have anatomic or functional asplenia. Persons whose spleens have been removed because of trauma or nonlymphoid tumors and persons who have inherited complement deficiencies have acceptable antibody responses to meningococcal vaccine; however, the clinical efficacy of vaccination has not been documented for these persons, and they may not be protected by vaccination (7,29). Research, industrial, and clinical laboratory personnel who routinely are exposed to N. meningitidis in solutions that may be aerosolized should be considered for vaccination.

Vaccination with the quadrivalent vaccine may benefit travelers to and U.S. citizens residing in countries in which N. meningitidis is hyperendemic or epidemic, particularly if contact with the local populace will be prolonged. Single-dose vials of the quadrivalent vaccine are now available and may be more convenient than multidose vials for use in international health clinics for travelers (30). Epidemics of meningococcal disease are recurrent in that part of sub-Saharan Africa known as the "meningitis belt," which extends from Senegal in the west to Ethiopia in the east (Figure_2) (31). Epidemics in the meningitis belt usually occur during the dry season (i.e., from December to June); thus, vaccination is recommended for travelers visiting this region during that time. Epidemics occasionally are identified in other parts of the world and recently have occurred in Saudi Arabia (during a Haj pilgrimage), Kenya, Tanzania, Burundi, and Mongolia. Information concerning geographic areas for which vaccination is recommended can be obtained from international health clinics for travelers, state health departments, and CDC (telephone: {404} 332-4559).

Primary Vaccination

For both adults and children, vaccine is administered subcutaneously as a single 0.5-mL dose. The vaccine can be administered at the same time as other vaccines but at a different anatomic site (i.e., deltoid muscle or buttocks). Protective levels of antibody are usually achieved within 7-10 days after vaccination.

Revaccination

Revaccination may be indicated for persons at high risk for infection (e.g., persons remaining in areas in which disease is epidemic), particularly for children who were first vaccinated when they were less than 4 years of age; such children should be considered for revaccination after 2-3 years if they remain at high risk. Although the need for revaccination of older children and adults has not been determined, antibody levels decline rapidly over 2-3 years, and if indications still exist for immunization, revaccination may be considered within 3-5 years.

PRECAUTIONS AND CONTRAINDICATIONS Reactions to Vaccination

Adverse reactions to meningococcal vaccine are mild and consist principally of pain and redness at the injection site, for 1-2 days. Estimates of incidence of mild-to-moderate local reactions have varied, ranging from infrequent to greater than 40% among vaccine recipients (32,33). Pain at the site of injection is the most commonly reported adverse reaction, and a transient fever might develop in less than or equal to 2% of young children.

Vaccination During Pregnancy

Studies of vaccination during pregnancy have not documented adverse effects among either pregnant women or newborns (34,35). In addition, these studies have documented high antibody levels in maternal and umbilical cord blood following vaccination during pregnancy. Antibody levels in the infants decreased during the first few months after birth; subsequent response to meningococcal vaccination was not affected (35). These observations have been confirmed in more recent studies of other polysaccharide vaccines administered during pregnancy (36). Based on data from studies involving use of meningococcal vaccines and other polysaccharide vaccines administered during pregnancy, altering meningococcal vaccination recommendations during pregnancy is unnecessary.

PROSPECTS FOR NEW MENINGOCOCCAL VACCINES

To enhance the immunogenicity and protective efficacy of A and C polysaccharides in infants and young children, methods similar to those used for H. influenzae type b conjugate vaccines have been applied to produce conjugate serogroups A and C vaccines (37,38). Capsular polysaccharides are being covalently linked to carrier proteins to convert the T-cell-independent polysaccharide to a T-cell-dependent antigen. The efficacy of these vaccines has not been evaluated.

Because the serogroup B capsular polysaccharide is poorly immunogenic in humans, vaccine development for serogroup B meningococci has focused on the outer membrane proteins as potential immunogens. The immunogenicity and protective efficacy of several outer membrane protein vaccines against several serogroup B meningococci have been evaluated recently. Evaluation of those vaccines documented estimated efficacies ranging from 57% to 83% in older children and adults (39-41). However, a subsequent study of one of these vaccines did not document efficacy in children less than 4 years of age, the group often at highest risk for disease (42). None of the currently available serogroup B meningococcal vaccines are licensed for use in the United States.

ANTIMICROBIAL CHEMOPROPHYLAXIS

Antimicrobial chemoprophylaxis of close contacts of sporadic cases of meningococcal disease is the primary means for prevention of meningococcal disease in the United States (Table_1). Close contacts include a) household members, b) day care center contacts, and c) anyone directly exposed to the patient's oral secretions (e.g., through kissing, mouth-to-mouth resuscitation, endotracheal intubation, or endotracheal tube management). The attack rate for household contacts exposed to patients who have sporadic meningococcal disease has been estimated to be four cases per 1,000 persons exposed, which is 500-800 times greater than for the total population (43). Because the rate of secondary disease for close contacts is highest during the first few days after onset of disease in the primary patient, antimicrobial chemoprophylaxis should be administered as soon as possible (ideally within 24 hours after the case is identified). Conversely, chemoprophylaxis administered greater than 14 days after onset of illness in the index case-patient is probably of limited or no value. Oropharyngeal or nasopharyngeal cultures are not helpful in determining the need for chemoprophylaxis and may unnecessarily delay institution of this preventive measure.

Rifampin is administered twice daily for 2 days (600 mg every 12 hours for adults, 10 mg/kg of body weight every 12 hours for children greater than or equal to 1 month of age, and 5 mg/kg every 12 hours for infants less than 1 month of age). Rifampin is effective in eradicating nasopharyngeal carriage of N. meningitidis (44). Rifampin is not recommended for pregnant women, because the drug is teratogenic in laboratory animals. Rifampin changes the color of urine to reddish-orange and is excreted in tears and other body fluids; it may cause permanent discoloration of soft contact lenses. Because the reliability of oral contraceptives may be affected by rifampin therapy, consideration should be given to using alternate contraceptive measures while rifampin is being administered.

In addition to rifampin, other antimicrobial agents are effective in reducing nasopharyngeal carriage of N. meningitidis. Ciprofloxacin in various dosage regimens is greater than 90% effective in eradicating nasopharyngeal carriage (45,46). A single 500-mg oral dose of ciprofloxacin is a reasonable alternative to the multidose rifampin regimen. Ciprofloxacin levels in nasal secretions far exceed the MIC90 for N. meningitidis following oral dosing (47). Ciprofloxacin is not generally recommended for persons less than 18 years of age or for pregnant and lactating women because the drug causes cartilage damage in immature laboratory animals. However, a recent international consensus report has concluded that ciprofloxacin can be used for chemoprophylaxis of children when no acceptable alternative therapy is available (48).

When ceftriaxone was administered in a single parenteral dose (an intramuscular dose of 125 mg for children and 250 mg for adults), it was 97%-100% effective in eradicating pharyngeal carriage of N. meningitidis (49,50). Thus, ceftriaxone (diluted in 1% lidocaine to reduce local pain after injection) is also a reasonable alternative for chemoprophylaxis.

Systemic antimicrobial therapy of meningococcal disease with agents other than ceftriaxone or other third-generation cephalosporins may not reliably eradicate nasopharyngeal carriage of N. meningitidis. If other agents have been used for treatment, the index patient should receive chemoprophylactic antibiotics for eradication of nasopharyngeal carriage before being discharged from the hospital (51).

CONCLUSIONS

N. meningitidis is the leading cause of bacterial meningitis in older children and young adults in the United States. The quadrivalent A, C, Y, and W-135 meningococcal vaccine available in the United States is recommended for control of serogroup C meningococcal disease outbreaks and for use among certain high-risk groups, including a) persons who have terminal complement deficiencies, b) persons who have anatomic or functional asplenia, and c) laboratory personnel who routinely are exposed to N. meningitidis in solutions that may be aerosolized. Vaccination also may benefit travelers to countries in which disease is hyperendemic or epidemic. Conjugate serogroup A and C meningococcal vaccines are being developed by using methods similar to those used for H. influenzae type b conjugate vaccines, and the efficacies of several experimental serogroup B meningococcal vaccines have been documented in older children and young adults.

Antimicrobial chemoprophylaxis of close contacts of patients who have sporadic cases of meningococcal disease is the primary means for prevention of meningococcal disease in the United States. Rifampin has been the drug of choice for chemoprophylaxis; however, data from recent studies document that single doses of ciprofloxacin or ceftriaxone are reasonable alternatives to the multidose rifampin regimen for chemoprophylaxis.

References

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2. CDC. Surveillance for diabetes mellitus -- United States, 1980-1989, and laboratory-based surveillance for meningococcal disease in selected areas -- United States, 1989-1991. MMWR 1993;42(No. SS-2):21-30.

3. Jackson LA, Tenover FC, Baker C, et al. Prevalence of Neisseria meningitidis relatively resistant to penicillin in the United States, 1991. J Infect Dis 1994;169:438-41.

4. CDC. Serogroup Y meningococcal disease -- Illinois, Connecticut, and selected areas, United States, 1989-1996. 1996;45:1010-13.

5. Jackson LA, Schuchat A, Reeves MW, Wenger JD. Serogroup C meningococcal outbreaks in the United States: an emerging threat. JAMA 1995;273:383-9.

6. CDC. Serogroup B meningococcal disease -- Oregon, 1994. MMWR 1995;44:121-4.

7. Figueroa JE, Densen P. Infectious diseases associated with complement deficiencies. Clin Microbiol Rev 1991;4:359-95.

8. Francke EL, Neu HC. Postsplenectomy infection. Surg Clin North Am 1981;61:135-55.

9. Pinner RW, Onyango F, Perkins BA, et al. Epidemic meningococcal disease in Nairobi, Kenya, 1989. J Infect Dis 1992;166:359-64.

10. Stephens DS, Hajjeh RA, Baughman WS, Harvey C, Wenger JD, Farley MM. Sporadic meningococcal disease in adults: results of a 5-year population-based study. Ann Int Med 1995;123:937-40.

11. Brundage JF, Zollinger WD. Evolution of meningococcal disease epidemiology in the U.S. Army. In: Vedros NA, ed. Evolution of meningococcal disease. 1st ed. vol I. Boca Raton, FL: CRC Press, 1987:5-25.

12. Peltola H, Kayhty H, Kuronen T, Haque N, Sarna S, Makela PH. Meningococcus group A vaccine in children three months to five years of age: adverse reactions and immunogenicity related to endotoxin content and molecular weight of the polysaccharide. J Pediatr 1978;92:818-22.

13. Gold R, Lepow ML, Goldschneider I, Draper TF, Gotschlich EC. Kinetics of antibody production to group A and group C meningococcal polysaccharide vaccines administered during the first six years of life: prospects for routine immunization of infants and children. J Infect Dis 1979;140:690-7.

14. Sippel JE. Meningococci. Crit Rev Microbiol 1981;8:267-302.

15. Taunay AE, Feldman RA, Bastos CO, Galvao PAA, Morais JS, Castro IO. Avalia§ o do efeito protetor de vacina polissacaridica antimeningocìcica do grupo C, em crian§as de 6 a 36 meses. Rev Inst Adolfo Lutz 1978;38:77-82.

16. Cochi SL, Markowitz LE, Joshi DD, et al. Control of epidemic group A meningococcal meningitis in Nepal. Int J Epidemiol 1987;16:91-7.

17. Rosenstein N, Levine O, Taylor J, et al. Persistent serogroup C meningococcal disease outbreak in a vaccinated population, Gregg County, Texas {Abstract G84}. In: 1996 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). American Society for Microbiology, 1996:185.

18. Griffiss JM, Brandt BL, Broud DD. Human immune response to various doses of group Y and W135 meningococcal polysaccharide vaccines. Infect Immun 1982;37:205-8.

19. Armand J, Arminjon F, Mynard MC, Lafaix C. Tetravalent meningococcal polysaccharide vaccine groups A, C, Y, W 135: clinical and serologic evaluation. J Biol Stand 1982;10:335-9.

20. Ambrosch F, Wiedermann G, Crooy P, George AM. Immunogenicity and side-effects of a new tetravalent meningococcal polysaccharide vaccine. Bull World Health Organ 1983;61:317-23.

21. Vodopija I, Baklaic Z, Hauser P, Roelants P, Andre FE, Safary

1. Reactivity and immunogenicity of bivalent (AC) and tetravalent (ACW135Y) meningococcal vaccines containing O-acetyl-negative or O-acetyl-positive group C polysaccharide. Infect Immun 1983;42:599-604.

22. Artenstein MS. Meningococcal infections. 5. Duration of polysaccharide-vaccine-induced antibody. Bull World Health Organ 1971;45:291-3.

23. Lepow ML, Goldschneider I, Gold R, Randolph M, Gotschlich EC. Persistence of antibody following immunization of children with groups A and C meningococcal polysaccharide vaccines. Pediatrics 1977;60:673-80.

24. Kayhty H, Karanko V, Peltola H, Sarna S, Makela PH. Serum antibodies to capsular polysaccharide vaccine of group A Neisseria meningitidis followed for three years in infants and children. J Infect Dis 1980;142:861-8.

25. Zangwill KM, Stout RW, Carlone GM, et al. Duration of antibody response after meningococcal polysaccharide vaccination in US Air Force personnel. J Infect Dis 1994;169:847-52.

26. Reingold AL, Broome CV, Hightower AW, et al. Age-specific differences in duration of clinical protection after vaccination with meningococcal polysaccharide A vaccine. Lancet 1985;2: 114-8.

27. CDC. Control and prevention of meningococcal disease and Control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1997;46(No. RR-5).

28. Peltola H, Makela PH, Kayhty H, et al. Clinical efficacy of meningococcus group A capsular polysaccharide vaccine in children three months to five years of age. N Engl J Med 1977;297:686-91.

29. Ruben FL, Hankins WA, Zeigler Z, et al. Antibody responses to meningococcal polysaccharide vaccine in adults without a spleen. Am J Med 1984;76:115-21.

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32. Lepow ML, Beeler J, Randolph M, Samuelson JS, Hankins WA. Reactogenicity and immunogenicity of a quadrivalent combined meningococcal polysaccharide vaccine in children. J Infect Dis 1986;154:1033-6.

33. Scheifele DW, Bjornson G, Boraston S. Local adverse effects of meningococcal vaccine. Can Med Assoc J 1994;150:14-5.

34. de Andrade Carvalho A, Giampaglia CM, Kimura H, et al. Maternal and infant antibody response to meningococcal vaccination in pregnancy. Lancet 1977;2:809-11.

35. McCormick JB, Gusm o HH, Nakamura S, et al. Antibody response to serogroup A and C meningococcal polysaccharide vaccines in infants born of mothers vaccinated during pregnancy. J Clin Invest 1980;65:1141-4.

36. Englund JA, Glezen WP, Turner C, Harvey J, Thompson C, Siber GR. Transplacental antibody transfer following maternal immunization with polysaccharide and conjugate Haemophilus influenzae type b vaccines. J Infect Dis 1995;171:99-105.

37. Anderson EL, Bowers T, Mink CM, et al. Safety and immunogenicity of meningococcal A and C polysaccharide conjugate vaccine in adults. Infect Immun 1994;62:3391-5.

38. Twumasi PA, Kumah S, Leach A, et al. A trial of a group A plus group C meningococcal polysaccharide-protein conjugate vaccine in African infants. J Infect Dis 1995;171:632-8.

39. Sierra GVG, Campa HC, Varcacel NM, et al. Vaccine against group B Neisseria meningitidis: protection trial and mass vaccination results in Cuba. NIPH Ann 1991;14:195-207.

40. Bjune G, H iby EA, Gronnesby JK, et al. Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway. Lancet 1991;338:1093-6.

41. Boslego JB, Garcia J, Cruz C. Efficacy, safety, and immunogenicity of a meningococcal vaccine group B (15:P1.3) outer membrane protein vaccine in Iquique, Chile. Vaccine 1995;13:821-9.

42. de Moraes JC, Perkins BA, Camargo MCC, et al. Protective efficacy of a serogroup B meningococcal vaccine in Sao Paulo, Brazil. Lancet 1992;340:1074-8.

43. The Meningococcal Disease Surveillance Group. Analysis of endemic meningococcal disease by serogroup and evaluation of chemoprophylaxis. J Infect Dis 1976;134:201-4.

44. Broome CV. The carrier state: Neisseria meningitidis. J Antimicrob Chemother 1986;18(suppl A):25-34.

45. Gaunt PN, Lambert BE. Single dose ciprofloxacin for the eradication of pharyngeal carriage of Neisseria meningitidis. J Antimicrob Chemother 1988;21:489-96.

46. Dworzack DL, Sanders CC, Horowitz EA, et al. Evaluation of single-dose ciprofloxacin in the eradication of Neisseria meningitidis from nasopharyngeal carriers. Antimicrob Agents Chemother 1988;32:1740-1.

47. Darouiche R, Perkins B, Musher D, Hamill R, Tsai S. Levels of rifampin and ciprofloxacin in nasal secretions: correlation with MIC90 and eradication of nasopharyngeal carriage of bacteria. J Infect Dis 1990;162:1124-7.

48. Schaad UB, Salam MA, Aujard Y, et al. Use of fluoroquinolones in pediatrics: consensus report of an International Society of Chemotherapy commission. Pediatr Infect Dis J 1995;14:1-9.

49. Schwartz B, Al-Tobaiqi A, Al-Ruwais A, et al. Comparative efficacy of ceftriaxone and rifampicin in eradicating pharyngeal carriage of group A Neisseria meningitidis. Lancet 1988;1:1239-42.

50. Judson FN, Ehret JM. Single-dose ceftriaxone to eradicate pharyngeal Neisseria meningitidis. Lancet 1984;2:1462-3.

51. 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.
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    Table_1
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    TABLE. Schedule for administering chemoprophylaxis against meningococcal disease
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    Drug                 Age group                Dosage          Duration and route of administration *
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    Rifampin           Children <1 mo 5 mg/kg every 12 hrs 2 days Children>= mo     10 mg/kg every 12 hrs                   2 days
                           Adults          600 mg every 12 hrs                    2 days
    
    Ciprofloxacin          Adults                 500 mg                       Single dose
    
    Ceftriaxone       Children <15 yrs 125 mg Single IM + dose Ceftriaxone Adults 250 mg Single IM dose * Oral administration unless indicated otherwise. + Intramuscular.="=====================================================================================================" 

    
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