Tratamiento de Meningitis

8/2/2019 Tratamiento de Meningitis

1/8

clinical practice

T h e n e w e n g l a n d j o u r n a l o f m e d i c i n e

n engl j med 355;14 www.nejm.org october 5, 20061466

Prevention of Meningococcal Disease

Pierce Gardner, M.D.

From the Department of Medicine andthe Graduate Program in Public Health,Stony Brook University School of Medi-cine, Stony Brook, NY.

N Engl J Med 2006;355:1466-73.Copyright 2006 Massachusetts Medical Society.

A previously healthy 18-year-old college freshman presented to an emergency depart-ment with acute onset of fever and headache. He was listless and in distress. His temper-ature was 40.0C, his pulse was 140 per minute, his blood pressure was 70/40 mm Hg,and his respirations were 35 per minute. Petechiae were noted over his thorax. Menin-gococcal septicemia was suspected (and subsequently confirmed by the growth of Neisseria meningitidis serogroup C isolated from blood). Despite the prompt adminis-tration of antibiotics and other support, the patients illness was fulminant and hedied 12 hours after the onset of the symptoms. Should he have previously receivedmeningococcal vaccine, and what measures should be taken to protect his close con-tacts and his community ?

T h e C l i n i c a l P r ob l e m

In the United States, the occurrence of a death from meningococcal disease is dev-astating to the family and the community of the person who died and elicits astrong demand for preventive measures from clinicians and the public health sec-tor. Preventive strategies include antimicrobial chemoprophylaxis for close contactsof patients with invasive meningococcal disease and, in certain circumstances, im-munization of the community with meningococcal vaccine.

Epidemiology of Neisseria meningitidis

Neisseria meningitidis commonly colonizes the nasopharynx in humans and is trans-mitted by direct contact with large-droplet respiratory secretions. In a 32-monthcommunity-based study, N. meningitidis was isolated from 18% of persons from

whom serial specimens were obtained. 1 Colonization may be transient, intermittent,or long-term, and the prevalence may increase in the presence of conditions such asconcomitant upper respiratory tract infection, crowded living conditions, and smok-ing. 2 Colonization induces an immunologic response to N. meningitidis (as do certainorganisms in the enteric flora that have cross-reacting antigens), so that by youngadulthood, the majority of people in the United States have measurable antibody to

the pathogenic serogroups of N. meningitidis (A, B, C, Y, and W-135).3-5

Invasive meningococcal disease is most often manifested by the development of meningitis or meningococcemia. The disease occurs most commonly in persons

who are seronegative and have newly acquired N. meningitidis .6 Entry into a new environment of crowded conditions (such as an educational institution or a mili-tary training camp) is the classic high-risk setting. For example, in a study of amilitary base involving 492 recruits, 3 13 recruits were initially seronegative andsubsequently became colonized with N. meningitidis ; invasive meningococcal dis-ease developed in 5 of them within 10 days after colonization was detected. Given

This Journal feature begins with a case vignette highlighting a common clinical problem.Evidence supporting various strategies is then presented, followed by a review of formal guidelines,

when they exist. The article ends with the authors clinical recommendations.

The New England Journal of MedicineDownloaded from nejm.org on April 5, 2012. For personal use only. No other uses without permission.

Copyright 2006 Massachusetts Medical Society. All rights reserved.


2/8

clinical practice

n engl j med 355;14 www.nejm.org october 5, 2006 1467

the short interval between the acquisition of theorganism and clinical infection, the immediatefocus of prevention is prompt chemoprophylaxisfor close contacts of a patient with invasive me-ningococcal disease.

Given the high rates of colonization withN. meningitidis , invasive meningococcal disease issurprisingly uncommon in the United States. Ap-proximately 2500 cases (0.5 to 1.1 per 100,000population) occur annually. The case fatality rateis approximately 10%, and substantial sequelaeoccur in about 11 to 19% of survivors (mainly be-cause of neurologic damage and complicationsresulting from disseminated intravascular coagu-lation). 2 The highest rate of disease occurs amongthe very young (Fig. 1), but 62% of cases occur inindividuals 11 years of age or older. Factors that increase colonization, such as an antecedent up-per respiratory tract infection, household crowd-ing, and both active and passive smoking, are as-sociated with an increased risk of meningococcaldisease. 2 Disease rates are higher among the poorand among black persons, 2 although these in-creases are attributable to other risk factors. Othergroups at increased risk for invasive meningococ-cal infection include persons with anatomical orfunctional asplenia or a deficiency in the terminalcommon complement pathway (C3 and C5 to C9),microbiologists routinely exposed to N. meningiti-dis , and travelers to regions where meningococ-

cal disease is epidemic or hyperendemic, suchas Saudi Arabia or sub-Saharan Africa. 7

Of the five pathogenic serogroups of N. men-ingitidis (A, B, C, Y, and W-135), those dominant inthe United States are B, C, and Y, each accountingfor approximately one third of the total cases, withB overrepresented among young children and Y overrepresented among the elderly. 2

Sporadic cases of meningococcal disease ac-count for more than 98% of cases. 2 Outbreaks(defined as 3 or more cases of the same serogroupbut not among persons in close contact with oneother, occurring within 3 months of one otherand resulting in an attack rate of greater than 10cases per 100,000 population) are uncommon but are highly disruptive to the community and tohealth care systems. Of 76 outbreaks identifiedin the United States during an 8-year period, ap-proximately 34% were community based and ap-proximately 65% occurred in colleges and univer-sities, primary and secondary schools, and nursinghomes. 2 Students recently arrived at college whoare living in dormitories have modestly elevatedrates of meningococcal disease (5.1 per 100,000population), but after the f irst year, the rates areno longer elevated and the overall rate among allundergraduate college students (0.7 per 100,000population) is lower than that among persons of similar age who are not enrolled in college (1.4per 100,000 population). 2

R a t e o

f M

e n i n g o c o c c a l

D i s e a s e

/ 1 0 0

, 0 0 0 P o p u

l a t i o n

8

9

7

6

4

3

1

5

2

0


3/8



S t r a t e g i e s a n d E v i d e n c e

Antimicrobial Chemoprophylaxis

The most urgent priority for prevention after a caseof meningococcal disease has been identified isto treat the patients close contacts with an effec-tive antimicrobial agent to eradicate potentialcolonization by N. meningitidis.The definition of close contact is not precise, but it is intended toinclude persons who have had prolonged (8 hoursor more) contact while in close proximity (3 ft isthe general limit for large-droplet spread) to thepatient or who have been direct ly exposed to thepatients oral secretions (e.g., through prolongedface-to-face contact, mouth-to-mouth resuscita-tion, kissing, or management of an endotrachealtube) within 1 week before the onset of the pa-tients symptoms until 24 hours after appropri-ate antimicrobial therapy has been initiated. Suchpersons typically include members of the house-hold and roommates, persons at a child-care cen-ter, and others who have had prolonged exposureto the infected patient (e.g., travelers on an air-plane seated next to the patient for more than8 hours). 8 Classmates and coworkers are not in-cluded unless they meet the criteria for close con-tact. Close contacts who have previously receivedmeningococcal vaccination should still be givenchemoprophylaxis, because the vaccines do not confer 100% protection and immunity wanes

with time.Table 1 summarizes the antimicrobial regimens

recommended by the Centers for Disease Con-

trol and Prevention (CDC) for prophylaxis on thebasis of their efficacy (90 to 95%) in eradicat-ing nasopharyngeal carriage of N. meningitidis andthe almost complete absence of secondary casesamong close contacts who have received antimi-crobial chemoprophylaxis. 2 Preliminary evidencesuggests that azithromycin may be similarly effec-tive,10 although confirmatory data are needed.

Ideally, chemoprophylaxis should be started within 24 hours after the index case has beenidentif ied, although diminishing levels of bene-fit may still be realized even with delays of up to2 weeks. 2 Chemoprophylaxis after 2 weeks addslittle benefit, presumably because the development of protective immunity in response to the colo-nizing N. meningitidis obviates the need for anti-microbial agents. Despite heavy community pres-sure to do something immediately in response toa death from meningococcal disease, mass chemo-prophylaxis in those who have not been in closecontact with an infected person is unwarrantedand is not recommended. However, in limitedsettings (e.g., a single school) in which cases of infection continue to occur, broad chemoprophy-laxis may be considered. 11 In such settings, alltargeted persons should receive chemoprophylaxisat the same time in order to avoid ping-pongreinfection.

Meningococcal Vaccines

Vaccination is recommended to provide preexpo-sure immunity in populations such as college stu-dents, adolescents, and other persons at an in-

Table 1. Regimens of Chemoprophylaxis against Meningococcal Disease.*

Medication Dose for Children Dose for Adults

Age,


4/8

clinical practice


creased risk for meningococcal infection (Table 2).It is also used to control outbreaks caused by sero-groups A, C, Y, and W-135 of N. meningitidis . Be-cause protective levels of antibody are not achieveduntil 7 to 10 days after the primary immuniza-tion (the period of greatest vulnerability after closecontact with an infected person), vaccination isnot an essential component of immediate dis-ease prevention for close contacts of patients withsporadic cases.

Two meningococcal vaccines, each containingantigens to serogroups A, C, Y, and W-135, are li-censed for use in the United States. A major limita-tion of these vaccines is that neither provides im-munity against serogroup B, which is responsiblefor approximately one third of cases of meningo-coccal disease. Both vaccines elicit protective lev-els of bactericidal antibody to all four serogroupsin more than 97% of recipients (as measured at 28 days). Both vaccines can be given with other

vaccines. Mild-to-moderate local reactions at theinjection site and minor systemic symptoms (i.e.,headache, fatigue, malaise, and low-grade fever)may occur after receipt of either vaccine.

The first vaccine, meningococcal polysaccha-ride vaccine (MPSV4 or Menomune, Sanofi Pasteur),has been available for more than 25 years. 12 It is approved for use in all age groups for whichmeningococcal vaccine is currently recommend-ed. The vaccine is safe and offers protection of approximately 90 to 95% for a limited period.However, the vaccine has several limitations. The

duration of protection is short (1 to 3 years inchildren younger than 5 years of age 13,14 and 3 to5 years in adolescents and adults). Like other poly-saccharide vaccines (e.g., against Streptococcus pneu-moniae and Haemophilus influenzae type b), it doesnot generate memory T cells, and attempts toboost protection with repeated vaccination may result in a diminished antibody response. 15,16 Also,like other polysaccharide vaccines, this menin-gococcal vaccine does not prevent mucosal colo-nization and therefore does not provide herdimmunity through interrupted transmission of N. meningitidis .17,18 These features make this vac-cine a reasonable option for persons requiringprotection for a limited time (travelers to an areaof endemic disease, college freshmen, at-risk per-sons in community outbreaks) but limit its use inbroad public health programs. The most impres-sive illustration of the protective effect of thepolysaccharide meningococcal vaccines has beenthe experience of the U.S. Army, which in theearly 1970s initiated the routine immunization of all recruits, thereby resulting in a sustained re-duction in the incidence of meningococcal dis-

ease (Fig. 2).19

The second vaccine, meningococcal conjugate vaccine A, C, Y, and W135 (MCV4 or Menactra,Sanofi Pasteur), was approved in January 2005 foruse in persons 11 to 55 years of age. It contains thesame antigens as those in the meningococcal poly-saccharide vaccine conjugated to 48 g of diphthe-ria toxoid. 2 This vaccine elicits an initial antibody

Table 2. Persons at Increased Risk for Meningococcal Disease for Whom Immunization Is Recommended.*

College freshmen living in dormitories

Microbiologists routinely exposed to Neisseria meningitidis

Populations in which an outbreak of meningococcal disease occurs

Military recruits

Persons with increased susceptibility (those with anatomical or functional asplenia or a terminal complement deficiency)Travelers to regions where N. meningitidis is hyperendemic (e.g., sub-Saharan Africa and Saudi Arabia) or epidemic

* The Advisory Committee on Immunization Practices also makes permissive recommendations for other persons notrecognized as being at increased risk but who may elect to be vaccinated. Such persons include adolescents not cov-ered in the initial rounds of immunization at the age of 11 years or on entry into high school, college students otherthan freshmen living in dormitories, and persons infected with the human immunodeficiency virus. The recommenda-tions do not specifically address other groups among whom an increased prevalence of meningococcal disease hasbeen noted, including black persons, persons of low socioeconomic status, those living in crowded conditions, andsmokers. Data are from the CDC. 2

Travelers may consult the CDC online (at www.cdc.gov/travel) or call the CDC Travelers Health Automated InformationLine (at 877-FYI-TRIP).




5/8


6/8

clinical practice


62% of the cases of meningococcal disease in theUnited States occur in children younger than 11

years of age, a comprehensive approach to prevent-ing meningococcal disease will need to addresschildren younger than 11 years. Conjugated poly-saccharide vaccines against H. influenzae type b andcertain pneumococcal serogroups have been shownto be effective in inducing immunity in childrenas young as 6 months of age and in lessening thetransmission of these pathogens to nonimmunizedpopulations. Preliminary studies suggest that theconjugated meningococcal vaccines elicit protec-tive immune responses in infants and young chil-dren, and the licensure of Menactra for use in

young children is anticipated. 23 However, the lack of an effective vaccine for serogroup B meningo-coccus (the cause of more than 50% of casesamong infants and young children) limits the po-tential effect of immunization strategies in in-fants and young children.

A theoretical concern is that a reduction inthe transmission of certain serogroups of N. men-ingitidis by vaccination may lead to replacement by other serogroups not covered by the vaccine(especially serogroup B). This was not observedin the United Kingdom after the broad immuni-zation of children with a serogroup C meningo-coccal vaccine. However, for both H. influenzae type b and the vaccine-related pneumococci, amodest degree of serogroup replacement has oc-curred since the implementation of routine pedi-atric immunization, and this possibility will needto be tracked for N. meningitidis .

Implementation of the plan for universal im-munization of adolescents has been hampered by

logistical shortcomings in reaching adolescent populations and by vaccine shortages. One man-ufacturer produces both Menomune and Menac-tra, making the manufacture of the vaccinespart icularly vulnerable to production problems.

As of February 2006, the development of theGuillainBarr syndrome in eight patients with-in 2 to 5 weeks after receipt of the conjugate vac-cine has been reported to the Vaccine AdverseEvent Reporting System of the CDC and the Foodand Drug Administration (FDA). 24 This overallrate appears to be within the expected backgroundincidence of the GuillainBarr syndrome (1 to2 cases per 100,000 population), but the timingis of concern and has prompted a warning in-cluded in the package insert for Menactra. TheFDA and the CDC consider the evidence insuffi-cient to establish a causal association or war-rant a change in the vaccine recommendations at this time. However, the GuillainBarr syndromedoes not appear to be a concern in relation tothe polysaccharide vaccine and pending furtherevaluation, some physicians may prefer to use thepolysaccharide vaccine when options exist.

Worldwide, the pattern of the meningococcalserogroups responsible for disease varies greatly according to region. In sub-Saharan Africa, majorepidemics of infection with serogroup A menin-gococcal disease are common and constitute amajor public health threat; limited use of a sero-group A polysaccharide vaccine in programs of epidemic control has achieved limited results. Theevaluation of a meningococcal A conjugate vaccinefor both routine immunization and epidemic con-trol is under way.

Table 3. Recommended Use of Meningococcal Vaccines in Previously Unvaccinated Persons.

General Population Persons at Increased Risk

A single dose of meningococcal conjugate vaccine isrecommended for persons 1112 yr of age or onentry into high school (approximately 15 yr of age).

A single dose of meningococcal conjugate vaccine ispreferred in persons 1155 yr of age.

A single dose of meningococcal polysaccharide vaccineis recommended for persons 210 yr of age or 55 yr

and is an acceptable alternative to meningococcalconjugate vaccine in patients 1155 yr of age.

Vaccination of persons younger than 2 yr of age is notrecommended.*

* Meningococcal polysaccharide vaccine may be used to elicit short-term protection against serogroup A disease in trav-elers to regions of endemic disease. For children 3 to 18 months of age, the vaccine is given in two doses 3 monthsapart, and in a single dose in children 19 to 23 months of age. Data are from the CDC. 2




7/8



G u i d e l i n e s

The recommendations of the ACIP for the use of meningococcal vaccines are summarized in Ta-bles 2 and 3. 2

C o n c l u s i o n s a n d

R e c o m m e n d a t i o n s

The rare but tragic case of death from meningo-coccemia described in the vignette could havebeen prevented by immunization with either of the two meningococcal vaccines. The conjugate

vaccine is currently recommended for use in ado-lescents and persons 11 to 55 years of age withdisorders or exposures putting them at an in-creased risk for meningococcal disease. (Becausethe approval of the meningococcal conjugate vac-cine is currently limited to use in persons of theseages, the meningococcal polysaccharide vaccineis preferred for persons 2 to 10 years of age andover 55 years of age.) Challenges to a comprehen-

sive program include the lack of coverage forserogroup B meningococcal disease by the cur-rent vaccines, vaccine shortages, logistical issues,and the high cost per case of illness or death pre-

vented.When a case of meningococcal disease occurs,

close contacts should be given chemoprophy-laxis, preferably within 24 hours after the iden-tification of the infection. Immunization is not an important component of the acute care of contacts in the setting of newly diagnosed infec-tion. However, the anxiety arising from a report of a case of meningococcal disease provides anopportunity to promote community compliance

with current recommendations. Population-basedimmunization programs are warranted in thecontrol of outbreaks of meningococcal diseaseinvolving infection with serogroups A, C, Y, andW-135.

No potential conflict of interest relevant to this article wasreported.

I am indebted to David Lin, M.D., for his contribution to theresearch and for his wisdom.

references

Greenfield S, Sheehe PR, Feldman HA.Meningococcal carriage in a populationof normal families. J Infect Dis 1971;123:67-73.

Prevention and control of meningo-coccal disease: recommendations of theAdvisory Committee on ImmunizationPractices (ACIP). MMWR Recomm Rep2005;54(RR-7):1-21.

Goldschneider I, Gotschlich EC, Ar-tenstein MS. Human immunity to the me-ningococcus. II. Development of naturalimmunity. J Exp Med 1969;129:1327-8.

Robbins JB, Myerowitz L, Whisnant JK,et al. Enteric bacteria cross-reactive withNeisseria meningitidis groups A and C andDiplococcus pneumoniae types I and II. Infect Immun 1972;6:651-6.

Edwards EA, Devine LF, SengbuschCH, Ward HW. Immunological investiga-tions of meningococcal disease. III. Brev-ity of group C acquisition prior to diseaseoccurrence. Scand J Infect Dis 1977;9:105-10.

Goldschneider I, Gotschl ich EC, Arten-stein MS. Human immunity to the menin-gococcus. I. The role of humoral antibod-ies. J Exp Med 1969;129:1307-26.

Health information for internationaltravel 2005-2006. Atlanta: Centers for Dis-ease Control and Prevention, 2005.

Guidelines for the management of air-line passengers exposed to meningococ-cal disease. Atlanta: Centers for Disease

1.

2.

3.

4.

5.

6.

7.

8.

Control and Prevention, 2000. (AccessedSeptember 11, 2006, at http://www.cdc.gov/travel/menin-guidelines.htm.)

Burstein GR, Berman SM, Blumer JL,Moran JS. Ciprofloxacin for the treatment of uncomplicated gonorrhea in adoles-cents: does the benefit outweigh the risk?Clin Infect Dis 2002;35:Suppl 2:S191-S199.

Girgis N, Sultan Y, Frenck RW Jr, El-Gendy A, Farid Z, Matezcun A. Azithromy-cin compared with rifampin for eradica-tion of nasopharyngeal colonization by Neisseria meningitidis.Pediatr Infect Dis J1998;17:816-9.

Zangwill KM, Schuchat A, Riedo FX,et al. School-based clusters of meningo-coccal disease in the United States: descrip-tive epidemiology and case-control analy-sis. JAMA 1997;277:389-95.

1999 Drug topics red book. Montvale,NJ: Medical Economics, 1999.

Reingold AL, Broome CV, HightowerAW, et al. Age-specific dif ferences in du-ration of clinical protection af ter vaccina-

tion with meningococcal polysaccharide A vaccine. Lancet 1985;2:114-8.Lepow ML, Goldschneider I, Gold R,

Randolph M, Gotschlich EC. Persistenceof antibody following immunization of children with groups A a nd C meningo-coccal polysaccharide vaccines. Pediatrics1977;60:673-80.

Borrow R, Joseh H, Andrews N, et al.Reduced antibody response to revaccina-

9.

10.

11.

12.

13.

14.

15.

tion with meningococcal serogroup A poly-saccharide vaccine in adults. Vaccine 2000;19:1129-32.

MacLennan J, Obaro S, Deeks J, et al.Immune response to revaccination withmeningococcal A and C polysaccharides inGambian children following repeated im-munization during early childhood. Vac-cine 1999;17:3086-93.

Hassan-King MK, Wall RA, Green- wood BM. Meningococcal carriage, menin-gococcal disease and vaccination. J Infect 1988;16:55-9.

Moore PS, Harrison LH, Telzak EE,Ajello GW, Broome CV. Group A meningo-coccal carriage in travelers returning fromSaudi Arabia. JAMA 1988;260:2686-9.

Department of Defense. Meningococ-cal disease among soldiers, U.S. Army,1964-1998. Med Surveill Mon Rep 2000;6(1):2-3.

Maiden MC, Stuart JM. Carriage of serogroup C meningococci 1 year aftermeningococcal C conjugate polysaccha-

ride vaccination. Lancet 2002;359:1829-31.Ramsay M, Andrews NJ, Trotter CL,

Kaczmarski EB, Miller E. Herd immunity from meningococcal serogroup C conju-gate vaccination in England: databaseanalysis. BMJ 2003;326:365-6.

Shepard CW, Ortega-Sanchez IR, Scott RD II, Rosenstein NE. Cost-effectivenessof conjugate meningococcal vaccination

16.

17.

18.

19.

20.

21.

22.




8/8

clinical practice


strategies in the United States. Pediatrics2005;115:1220-32.

MacLennan J, Obaro S, Deeks J, et a l.Immunologic memory 5 years after menin-23.

gococcal A/C conjugate vaccination in in-fancy. J Infect Dis 2001;183:97-104.

Update: Guillain-Barr syndromeamong recipients of Menactra meningo-24.

coccal conjugate vaccine United States,October 2005February 2006. MMWR MorbMortal Wkly Rep 2006;55:364-6.Copyright 2006 Massachusetts Medical Society.


C i h 2006 M h M di l S i All i h d

Tratamiento de Meningitis

Documents

Transcript of Tratamiento de Meningitis