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Meningococcal disease

Neisseria meningitidis infections estimated at 1400-2800 cases of meningococcal disease annually in the U.S.

Meningococcal disease occurs with an incidence of 0.2-14 for 100,000 population in industrialized countries.

1.2 million cases of invasive meningococcal invasive disease and 135,000 deaths worldwide, annually.

As with any gram-negative bacterium, N. meningitidis can infect a variety of sites.

Meningococcal meningitis is a form of bacterial meningitis. 

In meningococcal meningitis this is caused by the bacteria invading the cerebrospinal fluid and circulating through the central nervous system. 

Neisseria meningitidis the leading cause of meningitis in patients aged 2-18 years.

Meningococcus is pathogenic only in humans.

Manifests as meningitis in 49% of cases, meningococcemia in 33%, or pneumonia in 9% of cases.

Meningococcal pneumonia can appear during influenza pandemics and in military camps.

The patient with meningococcal meningitis typically presents with high fever, nuchal rigidity, Kernig’s sign, severe headache, vomiting, purpura, photophobia, chills, altered mental status, or seizures. 

Diarrhea or respiratory symptoms are less common. 

Petechiae are often also present, but do not always occur, so their absence should not be used against the diagnosis of meningococcal disease. 

Anyone with symptoms of meningococcal meningitis should receive intravenous antibiotics before the results of lumbar puncture, as delay in treatment worsens the prognosis.

Symptoms of meningococcemia are, at least initially, similar to those of influenza. 

The first symptoms include fever, nausea, myalgia, headache, arthralgia, chills, diarrhea, stiff neck, and malaise. 

Other later symptoms include: septic shock, purpura, hypotension, cyanosis, petechiae, seizures, anxiety, and multiple organ dysfunction syndrome, 

respiratory distress syndrome and altered mental status may also occur. 

Meningococcal sepsis has a greater mortality rate than meningococcal meningitis, neurologic sequelae is much common.

Meningococcal disease can cause life-threatening meningitis and sepsis conditions. 

It has a high mortality rate, if untreated, but is vaccine preventable.

It is best known as the cause of meningitis, but can also result in sepsis, which is more damaging and dangerous.

Meningitis and meningococcemia are major causes of illness, death, and disability in both developed an underdeveloped countries.

The case fatality rate ranges between 10 and 20 percent.

With meningitis, bacteria attack the the meninges,and Infected fluid from the meninges then passes into the spinal cord, causing symptoms including stiff neck, fever and rashes. 

Even with antibiotics, approximately 1 in 10 people who have meningococcal meningitis will die.

Many survivors of the disease lose a limb or their hearing, or experience permanent brain damage.

Meningococcal sepsis that affects the entire body. In this case, 

Bacterial toxins rupture blood vessels and can rapidly shut down vital organs.

The N. meningitidis bacterium contains disease-causing endotoxin. 

Many bacteria produce endotoxin, the levels produced by meningococcal bacteria are 100 to 1,000 times greater than normal. 

Bacteria multiply and move through the bloodstream, it sheds concentrated amounts of toxin, and the endotoxin directly affects the heart, reducing its ability to circulate blood, and also causes pressure on blood vessels throughout the body. 

Blood vessels hemorrhage in major organs like the lungs and kidneys are subsequently damaged.

Systemic antibiotics rapidly kill the bacteria but more toxin is released. It takes up to several days for the toxin to be neutralized from the body by using continuous intravenous fluid treatment and antibiotic therapy.

The most important form of prevention is a vaccine against N. meningitidis. 

The incidence of endemic meningococcal disease ranges from 1 to 5 per 100,000 in developed countries, and from 10 to 25 per 100,000 in developing countries.

During epidemics the incidence of meningococcal disease approaches 100 per 100,000. 

Meningococcal vaccines have sharply reduced the incidence of the disease in developed countries.

Serotypes A,B, C, Y and W-135 cause the majority of cases worldwide.

Occurs as a sporadic disease in industrialized nations with an incidence of 0.35 cases per 100,000 population in the US.

Major disease burden is in nonindustrialized countries.

Neisseria meningitidis colonizes a substantial proportion of the general population harmlessly, but in a very small percentage of individuals it can invade the bloodstream, affecting the entire body, most notably limbs and brain, causing serious illness. 

While meningococcal disease is not as contagious as the common cold, it can be transmitted through saliva and occasionally through close, prolonged general contact with an infected person.

Meningococcemia, like many other gram-negative blood infections, can cause disseminated intravascular coagulation (DIC).

Small bleeds into the skin cause the characteristic petechial rash, which appears with a star-like shape.

A rash can develop under the skin due to blood leakage which can develop into purple bruising. 

due to the release of toxins into the blood that break down the walls of blood vessels.

This is due to the release of toxins into the blood that break down the walls of blood vessels. A rash can develop under the skin due to blood leakage that may leave red or brownish pinprick spots,[3] which can develop into purple bruising. Meningococcal rash can usually be confirmed by a glass test in which the rash does not fade away under pressure.[4]

Meningitis[edit]

Major meningoccal meningitis epidemics occur every 10-12 years in the African meningitis belt, stretching from Senegal to Ethiopia.

Effective vaccines for capsular polysaccharides for meningococcal sero-groups A, C, W-135 and Y are available.

Serogroup B capsular polysaccharide is antigenic ally similar to human neural cell glycopeptides containing polysialic acid and Is poorly immunogenic In humans.

Antimicrobial prophylaxis for Neisseria meningitidis should be offered to close contacts of sporadic cases of meningitis: close contacts should be offered meningococcal vaccination if the outbreak strain is contained in the currently available meningococcal tetravalent conjugated vaccine, and antibiotic management with rifampin, ciprofloxacin or ceftriaxone.

Types B.C and Y are the only serotypes in the U.S.

Serotype B responsible for more than 50% of infections among infants.

Serotypes C, Y and W-135 account for 75% of cases among patients over the age of 11 years.

Retrospective review of 448 pediatric patients, with 103 deaths: early signs include aches, rash, flu-like symptoms, with first classic findings of rash that rapidly progressed to purpura, leg pain, cold hands and feet were worrisome signs of progression to shock, mental changes, seizures and coma can occur within 24-48 hours (Thompson).

Infection with Neisseria meningitis should be included in any acute illness associated with rapid progression of hemorrhagic rash, meningismus, altered mentation and sepsis.

Children less than 2 years of age and adolescents 15-19 years have a significant increased risk of invasive disease.

Case fatality rate of about 10%, with about 50,000 worldwide deaths per year.

Patients at increased risk include patients with asplenia and with complement deficiencies.

College students living in dormitories are at higher risk than the general population for acquiring the disease.

Early clinical features usually occurring within 12 hours of illness in children and adolescents include leg pain, cold hands and feet and abnormal skin color.

Vaccine MCV4 contains capsular polysaccharide from serogroups A, C, Y and W-135 and provides safe immunization among those aged 11-55 years, and is recommended for routine vaccination among children 11 year and older.

Twelve serogroups exist with six having the potential to cause a major epidemic – A, B, C, X, Y and W135 are responsible for virtually all cases of the disease in humans. 

Vaccines are currently available against all six strains, including the newest vaccine against serogroup B. 

Vaccines offer significant protection from three to five years for the plain polysaccharide vaccine Menomune, Mencevax and NmVac, and 

to more than eight years (conjugate vaccine Menactra).

Children 2–10 years of age who are at high risk for meningococcal disease such as certain chronic medical conditions and travel to or reside in countries with hyperendemic or epidemic meningococcal disease should receive primary immunization. 

Primary immunization against meningococcal disease with meningitis A, C, Y and W-135 vaccines is recommended for all young adolescents at 11–12 years of age and all unvaccinated older adolescents at 15 years of age. 

Although conjugate vaccines are the preferred meningococcal vaccine in adolescents 11 years of age or older, polysaccharide vaccines are an acceptable alternative if the conjugated vaccine is unavailable.

Primary immunization with meningitis A, C, Y and W-135 vaccines is recommended for college students who plan to live in dormitories, although the risk for meningococcal disease for college students 18–24 years of age is similar to that of the general population of similar age.

Routine primary immunization against meningococcal disease is recommended for most adults living in areas where meningococcal disease is endemic or who are planning to travel to such areas. 

Although conjugate vaccines are the preferred meningococcal vaccine in adults 55 years of age or younger, polysaccharide vaccines are an acceptable alternative for adults in this age group if the conjugated vaccine is unavailable. 

Since safety and efficacy of conjugate vaccines in adults older than 55 years of age have not been established to date, polysaccharide vaccines should be used for primary immunization in this group.

Health care people should receive routine immunization against meningococcal disease for laboratory personnel who are routinely exposed to isolates of N. meningitidis. 

Routine vaccination of health-care personnel is recommended, Any individual 11–55 years of age who wishes to reduce their risk of meningococcal disease may receive meningitis A, C, Y and W-135 vaccines and those older than 55 years of age. 

Under certain circumstances if unvaccinated health-care personnel cannot get vaccinated and who have intensive contact with oropharyngeal secretions of infected patients and who do not use proper precautions should receive anti-infective prophylaxis against meningococcal infection-2-day regimen of oral rifampicin or a single dose of IM ceftriaxone or a single dose of oral ciprofloxacin.

All military recruits routinely receive primary immunization against the disease.

Travelers to or residents of areas where N. meningitidis is highly endemic or epidemic are at risk of exposure should receive primary immunization against meningococcal disease.

HIV-infected individuals are likely to be at increased risk for meningococcal disease; HIV-infected individuals who wish to reduce their risk of meningococcal disease may receive primary immunization against meningococcal disease.

Protective levels of anticapsular antibodies are not achieved until 7–14 days following administration of a meningococcal vaccine, vaccination cannot prevent early onset disease in these contacts and usually is not recommended following sporadic cases of invasive meningococcal disease. 

Meningococcal infection is usually introduced into a household by an asymptomatic person. 

It is then spreads through the household, reaching infants usually after one or more other household members have been infected. 

Disease is most likely to occur in infants and young children who lack immunity to the strain of organism circulating and who subsequently acquire carriage of an invasive strain.

Preventing susceptible contacts from acquiring infection by directly inhibiting colonization. 

Close contacts include persons with intimate contact with the patient’s oral secretions such as through kissing or sharing of food or drink. 

In developed countries the disease transmission usually occurs in day care, schools and large gatherings where usually disease transmission could occur. 

The meningococcal organism is transmitted by respiratory droplets.

 It has been postulated that close contact is necessary for transmission. 

Meningitis occurs sporadically throughout the year, and since the organism has no known reservoir outside of man, asymptomatic carriers are usually the source of transmission.

Basic hygiene measures: handwashing and not sharing drinking cups, can reduce the incidence of infection by limiting exposure. 

All close contacts with the infected person can be offered antibiotics to reduce the likelihood of the infection spreading to other people. 

Chemoprophylaxis is commonly used for close contacts at high risk of carrying the pathogenic strains. 

Select vaccinations may be the most cost-effective means for controlling the transmission of the meningococcal disease.

Individuals with component deficiencies in the final common complement pathway (C3, C5-C9) are more susceptible to N. meningitidis infection than complement competent persons.

It is  estimated that the risk of infection is 7000 times higher  individuals with complement deficiencies.

Inherited properdin deficiency is related to an increased risk of contracting meningococcal disease.

Functional or anatomic asplenia may not efficiently clear encapsulated  meningitidis from the bloodstream.

Conditions associated with immunosuppression also may be at increased risk of developing meningococcal disease.

Rifampin, ceftriaxone, ciprofloxacin and penicillin are equally effective for the eradication of N. meningitidis in potential carriers, although rifampin was associated with resistance to the antibiotic following treatment. 

Whenever outbreaks of meningococcal disease occur in the US, chemoprophylaxis is the principal means of preventing secondary cases in household and other close contacts.

Meningitis A, C, Y and W-135 vaccines rarely may be used as an adjunct to chemoprophylaxis, where there is an ongoing risk of exposure to a serogroup contained in the vaccine is involved.

When a outbreak of meningococcal disease occurs, public health authorities will then determine whether mass vaccinations, with or without mass chemoprophylaxis, is indicated and delineate the target population to be vaccinated based on risk assessment.

Treatment:

When meningococcal disease is suspected, treatment must be started immediately and should not be delayed while waiting for confirmation.

Treatment in primary care usually involves prompt intramuscular administration of benzylpenicillin, and then an urgent transfer to hospital, ideally with neurological intensive and critical care units.

The antibiotics of choice are usually IV broad spectrum 3rd generation cephalosporins, e.g., cefotaxime or ceftriaxone. 

Benzylpenicillin and chloramphenicol are also effective. 

Supportive measures include IV fluids, oxygen, inotropic support, and management of raised intracranial pressure. 

Steroid therapy may help in some adult patients, but is unlikely to affect long term outcomes.

Complications following meningococcal disease can be divided into early and late groups. 

Early complications include: raised intracranial pressure, disseminated intravascular coagulation, seizures, circulatory collapse and organ failure. 

Late complications are: deafness, blindness, lasting neurological deficits, reduced IQ, and gangrene leading to amputations.

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