Meningococcal Infections

Meningococcal disease is a serious infection caused by ''Neisseria meningitidis'', also known as meningococcus, a gram negative diplococcus. Meningococcal disease includes meningitis, meningococcal septicemia, or a combination of both, which can be life-threatening and rapidly progressive. If left untreated, the disease has a high mortality rate; however, it is preventable through vaccination. Meningitis and meningococcal sepsis are major causes of illness, death, and disability in both developed and under-developed countries.

Meningococcal disease can be transmitted to others through saliva, close contact with an infected individual by inhaling respiratory air droplets. Initial symptoms may be subtle and similar to other bacterial infection, but can quickly progress to include fever, rash, body aches, photophobia and other complications. ''Neisseria meningitidis'' colonizes a substantial proportion of the general population without issues, but it can invade the bloodstream, affecting the entire body, most notably limbs and brain, causing serious illness in a small percentage of individuals.

The global incidence of meningococcal disease is relatively low, ranging from 0.0 to 10.2 per 100,000 however cases in the United States are rising.Sanford Guide to antimicrobial therapy 2014 44th edition Serotypes of the bacteria range from various countries, with serotype B accounting for most new cases worldwide. Meningococcal vaccines have sharply reduced the incidence of the disease in developed countries.

Vaccine has also shown to lessen cases of illness and their associated complications as well as death. Current vaccinations cover most of the bacterial strains that causes meningococcal disease. This has led to a decrease of incidence and burden from the disease.Treatment include supportive care, early administration of antibiotics and management of complications associated with infection. Ongoing research continues in an effort to understand specific aspects of meningococcal biology and host interactions; however, the development of improved treatments and effective vaccines is expected to depend on novel efforts by workers in many different fields.

Pathogenesis

Meningococcal disease causes life-threatening meningitis and sepsis conditions. In the case of meningitis, bacteria attack the lining between the brain and skull called the meninges. Infected fluid from the meninges then passes into the spinal cord, causing symptoms including stiff neck, fever and rashes. The meninges (and sometimes the brain itself) begin to swell, which affects the central nervous system.

Even with antibiotics, approximately 1 in 10 people who have meningococcal meningitis will die; however, about as many survivors of the disease lose a limb or their hearing, or experience permanent brain damage.Centers for Disease Control and Prevention. Meningococcal disease among college students: ACIP modifies recommendations for meningitis vaccination. Press release. 1999 Oct 20 The sepsis type of infection is much more deadly, and results in a severe blood poisoning called meningococcal sepsis that affects the entire body. In this case, bacterial toxins rupture blood vessels and can rapidly shut down vital organs. Within hours, patient's health can change from seemingly good to mortally ill.Jeeri R. Reddy and Thiombiano S. Rigobert. Infections à méningocoques Maladies infectieuses et Africa. West Africa. Med. Bull. 2007

The ''N. meningitidis'' bacterium is surrounded by a slimy outer coat that contains disease-causing endotoxin. While many bacteria produce endotoxin, the levels produced by meningococcal bacteria are 100 to 1,000 times greater (and accordingly more lethal) than normal. As the bacteria multiply and move through the bloodstream, it sheds concentrated amounts of toxin. The endotoxin directly affects the heart, reducing its ability to circulate blood, and also causes pressure on blood vessels throughout the body. As some blood vessels start to hemorrhage, major organs like the lungs and kidneys are damaged.

Patients with meningococcal disease are treated with a large dose of antibiotic. The systemic antibiotic flowing through the bloodstream rapidly kills the bacteria but, as the bacteria are killed, even more toxin is released. It takes up to several days for the toxin to be neutralized from the body by using continuous liquid treatment and antibiotic therapy.

Classification

Meningococcemia

Meningococcemia, also known as meningococcal septicemia, is an infection of the bloodstream. Meningococcemia makes up about approximately 20% of meningococcal disease cases. Symptoms of meningoccemia may include fever, low blood pressure as well as organ failure. Like many other gram-negative blood infections it can cause disseminated intravascular coagulation (DIC), which is the inappropriate clotting of blood within the vessels. DIC can cause ischemic tissue damage when upstream thrombi obstruct blood flow and hemorrhage because clotting factors are exhausted. Small bleeds into the skin cause the characteristic petechial rash, which appears with a star-like shape and mostly appears on the extremity of the body. 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, 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.

Meningoccemia can also lead to Waterhouse–Friderichsen syndrome, which is associated with disseminated intravascular coagulation or thrombosis of multiple organs and extremities and necrosis of adrenal glands.

Meningitis

Meningococcal meningitis is a form of bacterial meningitis caused by the ''Neisseria meningitidis'' bacteria. Meningitis is a disease caused by inflammation and irritation of the meninges, the membranes surrounding the brain and spinal cord. In meningococcal meningitis this is caused by the bacteria invading the cerebrospinal fluid and circulating through the central nervous system. The classic presentation of meningitis includes fever, neck stiffness, and altered mental status; however these symptoms are typically present in less than 50% of cases. Symptoms also differentiate between age groups, with older individuals presenting with altered mental status and localized neurological impairments and younger children showing general symptoms such as irritability, lethargy, or inability to feed.

Atypical types of meningococcal disease

''N. meningitidis'' can also result in atypical presentations throughout the body. Atypical types of meningococcal disease include septic arthritis, meningococcal pneumonia, pericarditis and acute gastrointestinal or GI symptoms.

GI symptoms from meningococcal disease includes nausea, vomiting and abdominal pain. These symptoms are rare but can occur during the initial phases of infection. These symptoms can often be misdiagnosed as gastroenteritis, also known as a inflammation of the stomach and intestines.

Septic arthritic is also associated with meningococcal disease. Septic arthritis caused by ''Neisseria meningitidis'' can appear as joint pain, redness, warmth, and limited movement. It typically affects just one joint—most often the knee—and is more common in very young or older individuals.

Meningococcal pneumonia can appear during influenza pandemics and in military camps. This is a multi-lobar, rapidly evolving pneumonia, sometimes associated with septic shock. With prompt treatment, the prognosis is excellent. Meningococcal pneumonia typical occurs in older individuals and found to be associated with serotype W of ''N. meningitidis''. Although rare, meningococcal pericarditis can occur.

Signs and symptoms

Meningitis

The patient with meningococcal meningitis typically presents with high fever, nuchal rigidity (stiff neck), Kernig's sign, severe headache, vomiting, purpura, photophobia, and sometimes chills, altered mental status, or seizures. Diarrhea or respiratory symptoms are less common. Petechiae are often also present, but do not always occur; their absence does not negate a diagnosis of meningococcal disease. Anyone with symptoms of meningococcal meningitis should receive intravenous antibiotics prior to the results of lumbar puncture being known, as delay in treatment can greatly worsen the prognosis.

Meningococcemia

Symptoms of meningococcemia are, at least initially, similar to those of influenza. Typically, the first symptoms include fever, nausea, myalgia, headache, arthralgia, chills, diarrhea, stiff neck, and malaise. Later symptoms include septic shock, purpura, hypotension, cyanosis, petechiae, seizures, anxiety, and multiple organ dysfunction syndrome. Acute respiratory distress syndrome and altered mental status may also occur. The petechial rash appear with the 'star-like' shape. Meningococcal sepsis has a greater mortality rate than meningococcal meningitis, but the risk of neurologic sequelae is much lower.

Diagnosis

Diagnosing meningococcal disease is vital; death can occur in a person within 6-12 hours with initial signs and symptoms.
Diagnosis includes clinical evaluation based on symptoms blood cultures, cerebrospinal fluid (CSF) analysis, basic metabolic panel, and possibly imaging.

Lumbar puncture is the gold standard for identifying a person has meningitis and rule out other causes of infection. This fluid covers the brain and spinal cord. This test should be completed unless a person has increased pressure in the brain such as swelling in the optic nerve or altered mental status.

Computer tomography (CT) can be used if diagnosis is unclear and if a person has depressed mental status.

Prevention

The most effective method of prevention is a vaccine against ''N. meningitidis''. Different countries have different strains of the bacteria and therefore use different vaccines. Twelve serogroups (strains) 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 a newer vaccine against serogroup B. The first vaccine to prevent meningococcal serogroup B (meningitis B) disease was approved by the European Commission on 22 January 2013.

Vaccines offer significant protection from three to five years (plain polysaccharide vaccine Menomune, Mencevax and NmVac-4) to more than eight years (conjugate vaccine Menactra).

Vaccinations

Children

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. Although safety and efficacy of the vaccine have not been established in children younger than 2 years of age and under outbreak control, the unconjugated vaccine can be considered.

Adolescents

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.

Adults

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.

Medical staff

Health care people should receive routine immunization against meningococcal disease for laboratory personnel who are routinely exposed to isolates of ''N. meningitidis''. Laboratory personnel and medical staff are at risk of exposure to ''N. meningitides'' or to patients with meningococcal disease. Hospital Infection Control Practices Advisory Committee (HICPAC) recommendations regarding immunization of health-care workers that 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 (i.e., 2-day regimen of oral rifampicin or a single dose of IM ceftriaxone or a single dose of oral ciprofloxacin).

USA military recruits

Because the risk of meningococcal disease is increased among USA's military recruits, all military recruits routinely receive primary immunization against the disease.

Travelers

Immunization against meningococcal disease is not a requirement for entry into any country, unlike yellow fever. Only Saudi Arabia requires that travelers to that country for the annual Hajj and Umrah pilgrimage have a certificate of vaccination against meningococcal disease, issued not more than 3 years and not less than 10 days before arrival in Saudi Arabia.

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

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. Although efficacy of meningitis A, C, Y and W-135 vaccines have not been evaluated in HIV-infected individuals to date, HIV-infected individuals 11–55 years of age may receive primary immunization with the conjugated vaccine. Vaccination against meningitis does not decrease CD4+ T-cell counts or increase viral load in HIV-infected individuals, and there has been no evidence that the vaccines adversely affect survival.Janoff EN, Tasker S, Opstad NL et al. Impact of immunization of recent HIV-1 seroconverters. Proceedings of ICAAC New Orleans 1996. Abstract No. I60

Close contacts

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. Unlike developed countries, in sub-Saharan Africa and other under developed countries, entire families live in a single room of a house.

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

Close contacts are defined as those persons who could have had intimate contact with the patient's oral secretions such as through kissing or sharing of food or drink. The importance of the carrier state in meningococcal disease is well known. In developed countries the disease transmission usually occurs in day care, schools and large gatherings where usually disease transmission could occur. Because the meningococcal organism is transmitted by respiratory droplets and is susceptible to drying, it has been postulated that close contact is necessary for transmission. Therefore, the disease transmission to other susceptible person cannot be prevented. 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.

Additionally, basic hygiene measures, such as handwashing and not sharing drinking cups, can reduce the incidence of infection by limiting exposure. When a case is confirmed, all close contacts with the infected person can be offered antibiotics to reduce the likelihood of the infection spreading to other people. However, rifampin-resistant strains have been reported and the indiscriminate use of antibiotics contributes to this problem. Chemoprophylaxis is commonly used to those close contacts who are at highest risk of carrying the pathogenic strains. Since vaccine duration is unknown, mass select vaccinations may be the most cost-effective means for controlling the transmission of the meningococcal disease, rather than mass routine vaccination schedules.

Chronic medical conditions

Persons with component deficiencies in the final common complement pathway (C3, C5-C9) are more susceptible to ''N. meningitidis'' infection than complement-satisfactory persons, and it was estimated that the risk of infection is 7000 times higher in such individuals. In addition, complement component-deficient populations frequently experience frequent meningococcal disease since their immune response to natural infection may be less complete than that of complement non-deficient persons.

Inherited properdin deficiency also is related, with an increased risk of contracting meningococcal disease. Persons with functional or anatomic asplenia may not efficiently clear encapsulated ''Neisseria meningitidis'' from the bloodstream Persons with other conditions associated with immunosuppression also may be at increased risk of developing meningococcal disease.

Antibiotics

An updated 2013 Cochrane review investigated the effectiveness of different antibiotics for prophylaxis against meningococcal disease and eradication of N. meningitidis particularly in people at risk of being carriers. The systematic review included 24 studies with 6,885 participants. During follow up no cases of meningococcal disease were reported and thus true antibiotic preventative measures could not be directly assessed. However, the data suggested that rifampin, ceftriaxone, ciprofloxacin and penicillin were equally effective for the eradication of ''N. meningitidis'' in potential carriers, although rifampin was associated with resistance to the antibiotic following treatment. Eighteen studies provided data on side effects and reported they were minimal but included nausea, abdominal pain, dizziness and pain at injection site.

Disease outbreak control

Meningitis A, C, Y and W-135 vaccines can be used for large-scale vaccination programs when an outbreak of meningococcal disease occurs in Africa and other regions of the world. Whenever sporadic or cluster cases or outbreaks of meningococcal disease occur in the US, chemoprophylaxis is the principal means of preventing secondary cases in household and other close contacts of individuals with invasive disease. Meningitis A, C, Y and W-135 vaccines rarely may be used as an adjunct to chemoprophylaxis,1 but only in situations where there is an ongoing risk of exposure (e.g., when cluster cases or outbreaks occur) and when a serogroup contained in the vaccine is involved.

It is important that clinicians promptly report all cases of suspected or confirmed meningococcal disease to local public health authorities and that the serogroup of the meningococcal strain involved be identified. The effectiveness of mass vaccination programs depends on early and accurate recognition of outbreaks. When a suspected 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 investigations. Treatment in primary care usually involves prompt intramuscular administration of benzylpenicillin, and then an urgent transfer to hospital (hopefully, an academic level I medical center, or at least a hospital with round the clock neurological care, ideally with neurological intensive and critical care units) for further care. Once in the hospital, 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, e.g., dopamine or dobutamine and management of raised intracranial pressure. Steroid therapy may help in some adult patients, but is unlikely to affect long term outcomes.

There is some debate on which antibiotic is most effective at treating the illness. A systematic review compared two antibiotics. There was one trial: an open label (not blinded) non-inferiority trial of 510 people comparing two different types of antibiotics; ceftriaxone (in which there were 14 deaths out of 247), and chloramphenicol (12 deaths out of 256). There were no reported side effects. Both antibiotics were considered equally effective. Antibiotic choice should be based on local antibiotic resistance information.

Prognosis

Complications

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.

Later complications of meningococcal disease can be physical, neurological, or psychological. Physical effects, most commonly following meningococcal septicemia, may include limb malformation or amputation. These outcomes are more frequently observed in children who have experienced invasive meningococcal disease. Neurological complications, typically associated with meningococcal meningitis, can include hearing loss, cognitive impairments, and seizures. Psychological effects, observed in children, include post-traumatic stress disorder (PTSD) and increased levels of anxiety.

Epidemiology

Africa

The importance of meningitis disease is as significant in Africa as HIV, TB and malaria. Cases of meningococcemia leading to severe meningoencephalitis are common among young children and the elderly. Deaths occurring in less than 24 hours are more likely during the disease epidemic seasons in Africa and Sub-Saharan Africa is hit by meningitis disease outbreaks throughout the epidemic season. It may be that climate change contributes significantly the spread of the disease in Benin, Burkina Faso, Cameroon, the Central African Republic, Chad, Côte d'Ivoire, the Democratic Republic of the Congo, Ethiopia, Ghana, Mali, Niger, Nigeria and Togo. This is an area of Africa where the disease is endemic: meningitis is "silently" present, and there are always a few cases. When the number of cases passes five per population of 100,000 in one week, teams are on alert. Epidemic levels are reached when there have been 100 cases per 100,000 populations over several weeks.

Further complicating efforts to halt the spread of meningitis in Africa is the fact that extremely dry, dusty weather conditions which characterize Niger and Burkina Faso from December to June favor the development of epidemics. Overcrowded villages are breeding grounds for bacterial transmission and lead to a high prevalence of respiratory tract infections, which leave the body more susceptible to infection, encouraging the spread of meningitis. IRIN Africa news has been providing the number of deaths for each country since 1995, and a mass vaccination campaign following a community outbreak of meningococcal disease in Florida was done by the CDC.

Florida

As of June 2022, there is an ongoing outbreak of the disease in Florida. The CDC has identified 26 cases of the disease. Seven deaths have been attributed to the disease.

History and etymology

From the Greek ''meninx'' (membrane) + ''kokkos'' (berry), meningococcal disease was first described by Gaspard Vieusseux during an outbreak in Geneva in 1805. In 1884, Italian pathologists Ettore Marchiafava and Angelo Celli described intracellular micrococci in cerebrospinal fluid, and in 1887, Anton Wiechselbaum identified the meningococcus (designated as ''Diplococcus intracellularis meningitidis'') in cerebrospinal fluid and established the connection between the organism and epidemic meningitis.

See also

* Endocarditis
* Pathogenic bacteria
* Waterhouse–Friderichsen syndrome
* African meningitis belt
* 2009–10 West African meningitis outbreak
* Meningococcal vaccine
* Meningitis Vaccine Project

References

Further reading

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External links

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{{DEFAULTSORT:Meningococcal Disease
Bacterial diseases
Bacterium-related cutaneous conditions
Causes of amputation
Sepsis
Vaccine-preventable diseases