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Guidelines for the Follow up of Invasive Meningococcal Disease

March 1997, Revised December 1988

Introduction

The organism, Neisseria meningitidis, is a Gram-negative diplococcus that causes meningococcal disease. Invasive meningococcal disease refers to N. meningitidis infection in the blood (meningococcemia), in the cerebral spinal fluid (CSF) (meningitis), or from any normally sterile body site, such as the lung or a joint. Historically, N. meningitidis has created high mortality epidemics throughout the world, and death rates have exceeded 50%. The development of antibiotics has significantly reduced but not eliminated mortality caused by this organism. It is estimated that fatality rate with early diagnosis and prompt medical treatment should be less than 10%.

Infection with N. meningitidis may give rise to a variety of clinical symptoms. The most frequent type of infection from this organism is an asymptomatic illness of the oro- or nasopharynx. In the most severe cases, individuals develop overwhelming septicemia and may die within two to eight hours of initial symptoms. The variability in clinical symptoms is due to the number of the bacteria present, the organs that become infected, possibly the infective strain, as well as other contributing factors. Meningococcal disease most often occurs in children less than five years of age; 45% of cases occur in children 2 years and under.

The most common systemic manifestation of meningococcal disease is meningitis. Individuals who develop acute illness from N. meningitidis often manifest a sudden onset of fever, intense headache, nausea and often vomiting, meningismus, and frequently a petechial rash. Occasionally, meningococcemia occurs when N. meningitidis enters the blood stream through the respiratory epithelium. When this happens, invasive disease may occur without simultaneous infection of the meninges. Meningococcemia should be suspected in individuals with an unexplained febrile illness associated with a non-blanching petechial rash and leukocytosis. Other illnesses resulting from infection from N. meningitidis include pneumonia, pericarditis, and arthritis.

In addition to early diagnosis and treatment of meningococcal cases, prompt public health attention is required to eliminate spread of the disease. Effective prophylactic treatment is available for contacts to cases of this disease.

The incidence rate for meningococcal disease cases is 1-1.5 per 100,000 population per year for sporadic cases. In Maryland, population of approximately five million 30-60 cases occur per year. Persons who are close contacts of people with meningococcal disease have a significantly greater risk of developing disease from this organism. According to the Centers for Disease Control and Prevention, the attack rate of meningococcal disease of household contacts exposed to patients who have sporadic meningococcal disease has been estimated to be 4 cases per 1,000 household contacts exposed per year, which is 500-800 times greater than for the total population. Because of this elevated rate, prophylactic antibiotics are given to contacts.

Asymptomatic colonization of the upper respiratory tract is frequent (5-20%) and provides the focus from which the organism is spread. N. meningitidis is transmitted by direct contact with secretions from the nose and throat, and via respiratory droplets from the nose and throat of an infected individual. Indirect transmission, such as through fomites, is insignificant. The incubation period ranges from approximately 2 to 10 days, but averages 3 to 4 days. Infected individuals are communicable until meningococci are no longer present in the discharges of the nose and mouth. The period of communicability of the meningococcus prior to acute illness is not well-established. Limited studies suggest that the majority of cases are infectious to others for only hours or a few days prior to the onset of symptoms. Based on these data, the period of asymptomatic transmission by those with acute illness is likely to be less than 10 days. In contrast, chronic nasopharyngeal carriers, the principle reservoir, remain asymptomatic and are protected from acute illness by serum antibodies. Outbreaks have occurred in child care centers, nursery schools, colleges, and military recruit camps.

Currently, N. meningitidis serogroups B and C are responsible for the majority of cases in the United States. Serotypes 2b and 15 are associated with serogroup B disease. Other serogroups, such as, groups A, X, Y, Z, 29-E and W-135 have also been shown to be associated with invasive meningococcal disease. Group A meningococci are found most frequently in outbreaks outside of the United States.

Diagnosis of invasive meningococcal disease is confirmed by the isolation of meningococci from blood, from CSF, or from other normally sterile body fluids, such as synovial fluid or pericardial fluid. Skin scrapings of petechiae may also yield positive cultures.

Procedures for Investigation

Clinical description

Meningococcal disease presents most commonly as meningitis and/or meningococcemia that may progress rapidly to purpura fulminans, shock, and death. However, other manifestations may be observed.

Isolation of Neisseria meningitidis from a normally sterile site

Probable: a positive antigen test in cerebrospinal fluid or clinical purpura fulminans in the absence of a positive blood culture

Confirmed: a clinically compatible case that is culture confirmed

Antigen test results in urine or serum are unreliable for diagnosing meningococcal disease.

a. Maryland Confidential Morbidity Report (DHMH-1140)

b. National Bacterial Meningitis and Bacteremia Case Report form (CDC 52.15 Rev. 02-93 version preferred) (see Attachment 1). Refer to the DHMH MERSS Manual for a copy of the form.

NOTE: Because N. meningitidis is one of the organisms that is monitored by Maryland's Bacterial Invasive Disease Surveillance (BIDS) System/Emerging Infections Program, the hospital infection control practitioner may have already completed the morbidity report and the CDC form.

2. Report the case immediately by telephone to:

DHMH, Office of Epidemiology and Disease Control Programs,
Division of Communicable Disease Surveillance
410-767-6712.

If DHMH receives the first report, we will fax the report to the local health department.

3. Assure that the N. meningitidis isolate is sent to the DHMH laboratory for serogroup determination:

DHMH, Laboratories Administration
201 West Preston Street
P.O. Box 2355
Baltimore, MD 21203

4. Enter into MERSS (see Section A for Case Definitions)

Mail the completed Maryland DHMH-1140 and CDC 52.15 forms to:

DHMH, Office of Epidemiology and Disease Control Programs, Unit #111
Division of Communicable Disease Surveillance
201 W. Preston Street
Baltimore, MD 21201-2323

5. Determine whether the case has been treated to eliminate nasopharyngeal carriage of N. meningitidis, i.e., determine if the case received rifampin or another medication listed in Tables 1 and 2, in addition to medication prescribed to treat acute illness.

6. Occasionally a person without meningococcal disease will be reported as having a throat culture positive for N. meningitis. In this situation, no treatment of the individual or contacts is warranted. No case form, morbidity card or MERSS report is needed.

Contacts are individuals who have had close contact with a case at some point during the period 10 days prior to the onset of illness in the case to 24 hours after the start of antibiotic treatment in the case. Contact is presumed to have occurred among:

a. household contacts (people who have stayed in the same household with the case)

b. child care contacts (children, employees, and volunteers in the same classroom as a case in institutions, such as group child care centers, family child care homes, or nurseries) and

c. other contacts (such as classmates, other child care contacts, friends, sexual partners, nurses, respiratory therapists, emergency medical personnel, etc.) who have been directly exposed to the case=s oral secretions through sharing food or beverages, kissing, mouth-to-mouth resuscitation, intubation, suctioning, etc.

a. The contact investigation should be conducted promptly. Ideally, prophylaxis should be started within 24 hours after the diagnosis of the case.

b. Identify all people who were contacts during the time period from 10 days prior to the onset of illness in the case to 24 hours after the start of antibiotic treatment of the case. Obtain information about contacts, including the time and type of exposure, and record it on the Contact Investigation Form (see Attachment 2).

c. Advise contacts to do the following as soon as possible:

i. Obtain appropriate chemoprophylaxis. Because the typical incubation period is 2-10 days, efforts to administer chemoprophylaxis are typically stopped 14 days after the case's onset date. It is considered to be of little value to administer chemoprophylaxis 14 days or more after the case's onset date. Local health departments may refer contacts to their private physician or dispense prophylactic antibiotics directly. See Tables 1 and 2 for dosing schedules of recommended antibiotics.

ii. Undergo an immediate medical evaluation in the event that they develop febrile illness in the 14 days following the occurrence of a case, and report the exposure to their medical care provider when evaluated.

d. Educate contacts. Consider distributing the Meningococcal Disease Fact Sheet to contacts (see Attachment 3).

e. In the setting of a child care facility (e.g., group child care center, family child care homes, or nursery) where contacts have been identified and can be notified within 10 days of when the case occurred:

i. Request that the administrator of the facility make a list of the names of all children and employees who are contacts of the case.

ii. Recommend prophylaxis for contacts. Consider giving a letter (see Attachment 4 for a sample letter) with the Meningococcal Disease Fact Sheet (and Rifampin Fact Sheet if rifampin is used) (see Attachments 3 and 6) to each contact and to the parent(s) of each child who was a contact.

iii. Alert the staff to be observant for children who develop high fever, rash, irritability, behavioral changes, stiff neck, body aches, chest pain, or breathing difficulty. Any child who develops any of these symptoms must be seen by a doctor immediately.

iv. Immediately report any other child who is diagnosed as having meningococcal disease to the local health department.

f. In the setting of a school (e.g., elementary, middle, high, college) where contacts have been identified and can be identified within 10 days of when the case occurred, consider sending a letter to inform parents and/or students of the occurrence. Possible recipients may include persons in the classroom, selected grades, the whole school, team members, dormitory residents. A sample letter for schools is attached (Attachment 5). (In the U.S., measures that have not been recommended for controlling serogroup C outbreaks include restricting travel to areas with a serogroup C outbreak, closing schools or colleges, or canceling sporting or social events [Reference 5, page 21]). Consult may be sought from EDCP Division of Outbreak Investigation.

g. Notify the Office of Epidemiology and Disease Control Programs, Division of Outbreak Investigation, (410) 767-6677, of any secondary invasive meningococcal cases.

Current recommendations regarding chemoprophylactic treatment of contacts exposed to a confirmed or probable case of N. meningitidis are as follows:

A. Ideally, prophylaxis should start within 24 hours after diagnosis of the case.

B. Treat contacts prophylactically if N. meningitidis is isolated from the case's blood, CSF, or a normally sterile site regardless of the presence or absence of symptoms in the case (i.e., confirmed case).

C. Treat contacts prophylactically if there are findings which support the diagnosis of meningococcal disease in the case (e.g., the detection of polysaccharide antigen by counterimmunoelectrophoresis or latex agglutination, the detection of gram-negative diplococci by microscopy, or purpura fulminans) in the absence of a bacteriological isolate of N. meningitidis (i.e., probable case).

D. In situations where the bacterial isolate of the case is not from a sterile site and the case exhibits upper or lower respiratory symptoms (e.g., pneumonia), discuss with the case physician whether N. meningitidis is the primary cause of illness in order to determine appropriate recommendations for prophylaxis. Treat contacts if the physician believes the illness is due to N. meningitidis (i.e., confirmed case).

E. Do not treat contacts prophylactically if N. meningitidis has been isolated from the throat or nasopharynx of a person who does not have symptoms of invasive disease (i.e., colonized person, carrier).

F. Chemoprophylaxis is not generally recommended for persons who are not close contacts (those not listed as household, child care, or other contacts in Item B.1. above, e.g., most school contacts, dormitory residents, etc.). These people may be informed, given fact sheets, and told to check with their physician if symptoms develop.

G. It is not necessary to obtain throat cultures from contacts. Chemoprophylaxis should be given to contacts immediately and should not be delayed while waiting for the results of contacts' throat cultures.

H. If agents other than rifampin, ciprofloxacin, or ceftriaxone are used in the treatment of meningococcal disease in the case, the case should receive one of the recommend prophylactic

agents before discharge from the hospital in order to reliably eradicate nasopharyngeal carriage of N. meningitidis.

Prophylactic antibiotics and dosing are outlined in Tables 1 and 2. Rifampin is the traditional drug of choice for prophylaxis, however, ciprofloxacin and ceftriaxone now are considered to be reasonable alternatives (Table 1). Sulfadiazine is recommended when an isolate is known to be sulfa-susceptible (Table 2).

Persons taking rifampin should be advised of potential side effects, such as, orange coloration of urine, stool, and tears. Additionally, individuals wearing soft contact lenses should not wear their lenses during the course of rifampin use and for 48 hours after the last dose. Individuals using oral contraceptives should be advised to use additional methods of birth control during that cycle (see Attachment 5).

Pregnant women should consult their doctors regarding recommendations for prophylactic treatment; ceftriaxone is the drug of choice if prophylaxis is needed.

Meningococcal Vaccine

In the United States, a quadrivalent meningococcal polysaccharide vaccine is available which stimulates immune responses to serogroups A, C, Y, and W-135. This vaccine is not routinely administered to civilians because of limitations in efficacy among children under 2 years of age and uncertainties about the duration of effect. The vaccine is recommended, however, for use in controlling outbreaks of group C meningococcal disease involving older children and adults. The efficacy of the vaccine in outbreaks caused by other serogroups is unknown. If used to elicit short-term protection against group A meningococcal disease, it may be used in children as young as 3 months of age [Reference 5, page 3]. Meningococcal vaccine is not indicated in outbreaks of serogroup B since serogroup B is not covered by the vaccine.

Antimicrobial chemoprophylaxis remains the primary preventive measure among contacts (defined in Item B.1. above) and should be administered regardless of plans for vaccine use. Seven to 10 days are needed following vaccination to develop protective levels of antibody. Specific recommendations for vaccine use in outbreak control (when the attack rate exceeds 10 cases per 100,000) should be made in consultation with the Division of Outbreak Investigation, EDCP, (410) 767-6677, who will refer to the ACIP Guidelines [Reference 5] and will contact the Centers for Disease Control and Prevention for advice.

View Table 1: Antibiotics recommended for chemoprophylaxis and eradication of nasopharyngeal carriage of N. meningitidis.

View Table 2. Sulfadiazine dosages for use in chemoprophylaxis where isolate is susceptible to sulfa drugs.

• American Academy of Pediatrics, Committee on Infectious Diseases Report of the Committee on Infectious Diseases (23rd ed.) Elk Grove Village, IL 1994.
• American Public Health Association.. Control of Communicable Diseases Manual (16th ed.). Washington, DC 1995.
• Centers for Disease Control and Prevention. Case Definitions for Public Health Surveillance. Morbidity and Mortality Weekly Report 1990; 39 (No. RR-13).
• Centers for Disease Control and Prevention. Laboratory-based surveillance for meningococcal disease in selected counties - United States, 1989-1991. Morbidity and Mortality Weekly Report 1993; 42(25): 498.
• Centers for Disease Control and Prevention. 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 Investigation Practices (ACIP). Morbidity and Mortality Weekly Report 1997; 46 (No. RR-5).
• Edwards, E. A., L. F. Devine, C. H. Sengbusch, H. W. Ward. 1977. Immunological Investigations of Meningococcal Disease. III. Brevity of group C acquisition prior to disease occurrence. Scand J Infect Dis 9:105-110.
• Last, J. M. (ed.). Public Health and Prevention Medicine (13th ed.) New York: Appleton-Century-Crofts, 1992.
• Mandell, G.L., Bennett, J.E. and Dolin, R. Principles and Practice of Infectious Diseases, 4th ed. New York: Churchill Livingston Inc., 1995.

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