Gram negative bacteria – Neisseria meningitides

Table II.

Risk group	Primary series	Booster dose
Age 11-18 ys	1 dose preferably at age 11 or 12 ys	At age 16 ys if primary dose at age 11 or 12 ys
		At age 16 through 18 years if primary dose at age 13 through 15 years
		No booster needed if primary dose on or after age 16
HIV infected persons	2 doses, 2 months apart	At age 16 years if primary dose at age 11 or 12 years
		At age 16 through 18 years if primary dose at age 13 through 15 years
		No booster needed if primary dose on or after age 16 years
Persons aged 2 through 55 years withComplement deficiency of functional or anatomical asplenia++	2 doses, 2 months apart	Every 5 years
		At the earliest opportunity if a 1- dose primary series administered, then every 5 years
Persons aged 2 through 55 years with prolonged increase risk of exposure+	1 dose	Persons aged 2 through 6 years: after 3 years
		Persons aged 7 years or older: after 5 years*

Caution

There have been reported cases of Guillain-Barre within 2-5 weeks after receipt of the conjugate vaccine. The overall rate appears to be within the expected background incidence of Guillain-Barre syndrome (1 to 2 cases per 100,000 population), but the timing is of concern and has prompted a warning included in the package insert of the MCV4 vaccine (Menactra)

The FDA and the CDC consider evidence insufficient to establish a casual association or warrant a change in the vaccine recommendations at this time.

However, the syndrome does not appear to able a concern in relation to the polysaccharide vaccine and some physicians may prefer to use polysaccharide vaccine when options exists

Identification of an outbreak

An outbreak of meingococcal disease is a public health crisis that calls for a rapid, coordinated public health response.

Changes that suggest an outbreak is evolving include:

• Clustering of cases within an age or social group;

• Shift in disease from children under five years to older children and adolescents;

• Phenotypic and genetic similarity among the strains causing disease.

For a primary attack rate to be calculated, all confirmed cases of the same serogroup should be summed; secondary cases should be excluded and each set of co-primary cases counted as one case. Because attack rates are calculated both to characterize the risk for disease among the general population and to determine whether overall rates have increased, related cases (secondary and co-primary) should not be included. From an epidemiologic perspective, secondary and co-primary cases can be considered as representing single epidose of disease with direct spread to one or more close contact(s),which is consistent with endemic disease

If three or more cases have occurred in either an organization or a community-based outbreak during <3 months (starting at the time of the first confirmed or probable case), a primary attack rate should be calculated. Because of the limited number of cases typically involved and the seasonal patterns of meningococcal disease (more cases occur during fall than other times of the year), rate calculations should not be annualized. The following formula is used to calculate attack rates:

Attack rate per 100,000 = [(number of primary confirmed or probable cases during a 3-month period)/ (number of population at risk )] x 100,000.

Genotyping date can allow identification of an outbreak strain and help to better define the extent of the outbreak. If strains from a group of patients are unrelated by genotyping, the group of cases most likely does not represent an outbreak. Because molecular subtyping testing might not be readily available or accessible, initiation of outbreak control efforts should not be delayed until genotyping results are available.

What are the consequences of ignoring gram negative bacteria – Neisseria meningitides?

Each year, an estimated 2,400-3,000 case of meningococcal disease occurs in the United States, a rate of 0.8-1.3/100,000 population.

N. meningitidis is one of the leading causes of bacteremic meningitis in the United States.

Despite the continued antibiotic susceptibility of meningococcus to multiple widely available antibiotics, including penicillin, the case-fatality ratio for meningococcal disease is 10%-14%.

Neisseria meningitidis can be classified into 13 serogroups based on the immunologic reactivity of their capsular polysaccharides. Serogroups B, C and Y each cause approximately one third of meningococcal disease cases in the United States. The proportion of cases caused by each serogroup varies by age; serogroup B causes over 50 % of cases in infants younger than 1 year of age, while segrogroups C,Y, and W135 cause 75 % of meningococcal disease in those 11 years and older.

In the United States, >98 % of cases of meningococcal disease are sporadic; however, since 1991, the frequency of localized outbreaks has increased.

Type A is the most common cause within the meningitis belt of Sub-Saharan Africa (a region of savanna that extends from Ethiopia in the east to Senegal in the west), accounting for an estimated 80-85 % of all cases. This disease frequently occurs in epidemics during the hot and dry weather (December to March).

Persons who have deficiencies in the terminal common complement pathway (C3, C5-C9) and those with asplenia are at increased for acquiring meningococcal disease. Antecedent viral infection, household crowding, chronic underlying illness, and both active and passive smoking also are associated with increased risk for meningococcal disease.

During outbreaks, bar or nightclub patronage and alcohol use also have been associated with higher risk for meningococcal disease.

Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis. Several factors make meningococcal disease a matter of public health importance. First it is a communicable disease associated with notable morbidity and mortality. Second, isolated meningococcal cases and outbreaks often causes serious medical and social stress in communities and are associated with increased costs, both economic and social. Finally, each case of meningococcal disease requires a public health response.

Breaches in infection control, notification delays, and lack of worker exposure assessment and post exposure chemoprophylaxis (PEP) can contribute to secondary cases.

Employers should provide adequate infection-control training to staff member, PEP to exposed workers, and report notifiable disease promptly.

What other information supports the conclusions of studies on gram negative bacteria – Neisseria meningitides, e.g., case-control studies and case series?

A prospective surveillance study with nested case control study of US college students with meningococcal infection from September 1, 1998, to August 31, 1999 showed that freshmen living in dormitories had the highest incidence rate at 5.1 per 100,000 compared to 1.4 per 100,000 for the general population. Of the 79-case patients for whom information was available, 54 (68%) had illness due to vaccine-preventable meningococcal serogroups supporting the data from the Advisory Committee on Immunization Practices (ACIP).

A large retrospective study was performed to summarize the evidence for the role of antibiotics in preventing further cases of meningococcal disease through chemoprophylaxis given to the index patient, household contacts and children in day care settings after a single case. The main outcome was to measure subsequent cases of meningococcal disease 1-30 days after onset of disease in the index patient. The conclusion was that the risk of meningococcal disease in household contacts could be reduced by an estimated 89 % if they take antibiotics known to eradicate meningococcal carriage. Chemoprophylaxis should be recommended for the index patient and all household contacts.

Summary of current controversies.

Nasopharyngeal carriage

There are no recommendations for eradicating nasopharyngeal carriage in the community outside of an outbreak or a patient with invasive meningococcal disease. There are three problems with attempting to eliminate nasopharyngeal carriage in the community:

• Spontaneous loss and acquisition of carriage is common. This was illustrated in a study in military recruits in which 34% experienced one or more change in carrier status over time

• Recurrent colonization may occur after prophylaxis. In a community-wide prophylaxis program in a semi-closed kibbutz population in Israel, the colonization rate of group B meningococcus dropped from 4.6% at baseline to 0% at 3 weeks; it then rose to 0/5% at 6 months and 3.9% (similar to the baseline level) at one year

• Antimicrobial prophylaxis has no proven clinical efficacy outside of an outbreak. The meta-analysis cited above included trials in healthy carries. Clinical efficacy of eradication could not be assessed since there were no cases of disease following antibiotics or placebo

Some national policies also recommended chemoprophylaxis to the index patient before discharge from hospital, on the premise that the pathogenic strain may otherwise be reintroduced by the index patient into the household. However, contradictory findings regarding carriage of the pathogenic meningococcal strain after full antibiotic treatment of the index patient are reflected in different recommendations. For example, policy in Denmark, Norway, and Sweden does not recommend prophylaxis for the index patient, whereas it is recommended in the United Kingdom, Canada, the United States, Spain and Germany.

In the United States, chemoprophylaxis is recommended to the index patient if systemic antimicrobial therapy of meningococcal disease with agents other than ceftriaxone or other third-generation cephalosporins were used given that it might not reliably eradicate nasopharyngeal carriage of N. meningitidis.

Mass chemoprophylaxis

Despite heavy community pressure to “do something” immediately in response to a death from meningococcal disease, mass chemoprophylaxis in those who have not been in close contact with an infected persons is unwarranted and is not recommended.

Administration of antibiotics to substantial populations is not recommended to control large outbreaks of disease.

Disadvantages of mass chemoprophylaxis include cost of the drug and administration, difficulty of ensuring simultaneous administration of drugs to substantial populations, drug side effects, and emergence of resistant organisms. In addition, multiple sources and prolonged risk for exposure make this approach impractical and unlikely to succeed. In the majority of outbreak settings, these disadvantages outweigh the possible benefit in disease prevention. However, in outbreaks involving limited populations (e.g., an outbreak in a single school), administration of chemoprophylaxis might be considered, especially in serogroup B outbreaks, for which available vaccines are not effective. When making a decision about initiating mass chemoprophylaxis in these settings, public health officials should consider not only the potential for prevention of new cases but also the logistics, cost, and potential for developing antimicrobial resistance.

However, in limited settings (e.g., a single school) in which cases of infection continue to occur, broad chemoprophylaxis may be considered. In such settings, all targeted persons should receive chemoprophylaxis at the same time in order to avoid “ping-pong” reinfection.

Source control

In the United States, measures that have not been recommended for control of meningococcal disease outbreaks include restricting travel to areas with an outbreak, closing schools or universities, or canceling sporting or social events.

What is the impact of gram negative bacteria – Neisseria meningitides and the need for control, relative to infections at other sites or from other specific pathogens?

Invasive infections caused by Neisseria meningitis are a serious public health problem worldwide and have a heavy economic impact. The incidence of invasive disease due to Neisseria meningitids is highly variable according to geographical area and serogroup distribution.

The occurrence of a death form meningococcal disease is devastating to the family and the community of the person who died and elicits a strong demand for preventive measure from clinicians and the public health sector.

Preventive strategies include antimicrobial chemophrohylaxis for close contacts of patients with invasive meningococcal disease, and in certain circumstances, immunization of the community with meningococcal vaccine.

Summary of research relevant to gram negative bacteria – Neisseria meningitides.

See Table III.