Meningococcal disease

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 suffer from meningococcal meningitis will die; however, a similar proportion of survivors are affected by limb loss, hearing impairment, or permanent brain damage. 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, patients' health can change from seemingly good to mortally ill. 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==

Invasive meningococcal disease (IMD) is a typically a more severe form of the disease; it is a major cause of sepsis and meningitis. Meningococcemia Meningococcemia, also known as meningococcal septicemia, infection, or sepsis, 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. 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. 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 arthritis 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 epidemics; A, B, C, X, Y and W135 are responsible for virtually all cases of the disease in humans. Vaccines are currently available against all of these six strains. 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. In the UK, infants are routinely vaccinated against serotype B. 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. United States military recruits Because the risk of meningococcal disease is increased among United States's military recruits, all military recruits routinely receive primary immunization against the disease. 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 underdeveloped 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 persons 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. 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. 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==

, who had all four limbs partially amputated aged seven months due to meningococcal B disease. 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. Europe Asia Americas From 2021 to 2023 there was an outbreak of the disease in Florida primarily in MSM caused by serogroup C. == 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 Weichselbaum identified the meningococcus (designated as Diplococcus intracellularis meningitidis) in cerebrospinal fluid and established the connection between the organism and epidemic meningitis. == See also ==