Meningococcal Disease

Meningococcal disease

Meningococcal disease describes infections caused by the bacterium Neisseria meningitidis (also termed meningococcus). It carries a high mortality rate if untreated. Whilst best known as a cause of meningitis, wide spread blood infection (sepsis) is more damaging and dangerous. Meningitis and Meningococcal septicemia are major causes of illness, death and disability in both developed and under developed countries worldwide.

The disease's host/pathogen interaction is not fully understood. The pathogen originates harmlessly in a large number of the general population, but thereafter can invade the blood stream and the brain, causing serious illness. Over the past few years, experts have made an intensive effort to understand specific aspects of meningococcal biology and host interactions, however the development of improved Meningococcal disease treatments and effective vaccines will depend on novel efforts by workers in many different fields.[1]

The incidence of endemic meningococcal disease during the last 13 years 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 1000 per 1,000,000. There are approximately 2,600 cases of bacterial meningitis per year in the United States, and on average 333,000 cases in developing countries. The case fatality rate ranges between 10 and 20 per cent.[2].

While Meningococcal disease is not as contagious as the common cold (which is spread through casual contact), it can be transmitted through saliva and occasionally through close, prolonged general contact with an infected person.

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 including stiff neck, fever and rashes. The meninges (and sometimes the brain itself) begin to swell, which affects the central nervous system.

1 in 10 victims of meningococcal meningitis will die, however survivors of the disease are often left deaf or with 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, patient's health can change from seemingly good to mortally ill.[3].

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 suffering from 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[4].

Types of infection

Septicemia

Meningococcal septicemia, like many gram-negative blood infections, can cause disseminated intravascular coagulation (DIC), a condition where blood starts to clot throughout the body, sometimes causing ischemic tissue damage. DIC also causes bleeding, when the clotting factors are used up, causing the characteristic purpuric rash.

Meningitis

Meningococcal meningitis is a consequence of bacteria entering the cerebrospinal fluid (CSF) and irritating the meninges - the membranes that line the brain and spinal cord. Sub-Saharan Africa, Americas, Western Europe, UK and Ireland face multifarious challenges, 200 years after the discovery of bacterial meningitis[5].

Other types

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

Meningococcal pneumonia can appear during influenza pandemics and in military camps. This is a multilobar, rapidly evolving pneumonia, sometimes associated with septic shock. With prompt treatment with penicillin or chloramphenicol, the prognosis is excellent. Pericarditis can appear, either as a septic pericarditis with grave prognosis or as a rective pericarditis in the wake of meningitis or septicaemia. Myocarditis can be a complication of meningococcemia and can be contributive to shock seen in this form of disease. Pharyngitis and conjunctivitis can also appear and can constitute the portal of entry for the bacterium. Septic arthritis due to N. meningitidis can be seen, usually accompanying disseminated infection. Other forms of disease can rarely be seen, like osteomyelitis, endophthalmitis and urethritis.

Prevention

The most important form of prevention is a Meningococcal vaccine against N. meningitidis. Different countries have different strains of the bacteria and therefore use different vaccines. Five serogroups, A, B, C, Y and W135 are responsible for virtually all cases of the disease in humans. Vaccines are currently available against four of the five strains, and a vaccine against the B strain is in development. Menactra, Menomune of Sanofi-Aventis, Mencevax of GlaxoSmithKline and NmVac4-A/C/Y/W-135 (has not been licensed in the US) of JN-International Medical Corporation are the commonly used vaccines. Unfortunately, there is currently no evidence that any of the current vaccines offer significant protection beyond 18 months (plain polysaccharide vaccine Menomune, Mencevax and NmVac-4) to three years (polysaccharide protein conjugate vaccine Menactra, NmVac4-A/C/Y/W-135 - DT.[13][14]

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. Safety and efficacy of Meningitis A,C,Y and W-135 vaccines have not been established in children younger than 11 years of age; however, clinical studies in children 2–10 years of age have been recommended [15].[16][17].[18].

Children and adolescents 11 years of age or older: It is recommend that primary immunization against meningococcal disease with Meningitis A,C,Y and W-135 vaccines for all young adolescents at 11–12 years of age and all unvaccinated older adolescents at 15 years of age. Although Meningitis A,C,Y and W-135 vaccines are the preferred meningococcal vaccine in adolescents 11 years of age or older, Meningitis A,C,Y and W-135 vaccines are an acceptable alternative if the conjugated vaccine is unavailable.[16][17][19][20]

Adults: College Students who plan to live in dormitories receive primary immunization with Meningitis A,C,Y and W-135 vaccines. Although the risk for meningococcal disease for is similar to 18–24 years of age that for the general population of similar age. The college students consider vaccination against meningococcal disease to reduce their risk for the disease and stated that college health-care providers should take a proactive role in providing information about meningococcal disease to students and their parents.[21] Routine primary immunization against meningococcal disease is recommended for most adults live in endemic areas and planning to travel such areas. Although Meningitis A,C,Y and W-135 vaccines are the preferred meningococcal vaccine in adults 55 years of age or younger, Meningitis A,C,Y and W-135 vaccines are an acceptable alternative for adults in this age group if the conjugated vaccine is unavailable. Since safety and efficacy of Meningitis A,C,Y and W-135 vaccines in adults older than 55 years of age have not been established to date, Meningitis A,C,Y and W-135 vaccines should be used for primary immunization in this group.[16][17]

Medical staff and laboratory personnel: 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 rifampin or a single dose of IM ceftriaxone or a single dose of oral ciprofloxacin).[16][22]

Military recruits: Because the risk of meningococcal disease is increased among military recruits, all military recruits routinely receive primary immunization against the disease.[23]

Travelers and tourists: Immunization against meningococcal disease is not a requirement for entry into any country, unlike Yellow fever. Only Saudi Arabia require that travelers to their 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.[17][24]

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.[22] 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.[22] Vaccination against meningitis do 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.[25][26][27]

Household and other close contacts of individuals with invasive 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. Unlike, developed countries, in sub-Saharan Africa and other under developed countries, entire family live in a single room of a house.[28][29] 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.[30] By preventing susceptible contacts from acquiring infection by directly inhibiting colonization. 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.[31] 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. Vaccinations are the only answer for reducing the transmission of the Meningococcal disease.[32][33]

Meningococcal Disease
Campylobacter Infections Pneumonia Carcinoid Tumors Spleen Diseases Bacterial vaginosis Toxoplasmosis Meningococcal Disease Vaginal Diseases Stomach cancer Ingrown Nail Giardiasis Cardiogenic shock Scoliosis Chronic Diarrhea Urinary Tract And Bladder Infections Aortic Stenosis Mitral Valve Prolapse Colorectal cancer Liver cancer Yersinia Enterocolitica Kaposi's Sarcoma Leukemia, Adult Acute Shigellosis Sickle-cell disease Adenoviridae Coming Soon	Meningococcal disease Meningococcal disease describes infections caused by the bacterium Neisseria meningitidis (also termed meningococcus). It carries a high mortality rate if untreated. Whilst best known as a cause of meningitis, wide spread blood infection (sepsis) is more damaging and dangerous. Meningitis and Meningococcal septicemia are major causes of illness, death and disability in both developed and under developed countries worldwide. The disease's host/pathogen interaction is not fully understood. The pathogen originates harmlessly in a large number of the general population, but thereafter can invade the blood stream and the brain, causing serious illness. Over the past few years, experts have made an intensive effort to understand specific aspects of meningococcal biology and host interactions, however the development of improved Meningococcal disease treatments and effective vaccines will depend on novel efforts by workers in many different fields.[1] The incidence of endemic meningococcal disease during the last 13 years 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 1000 per 1,000,000. There are approximately 2,600 cases of bacterial meningitis per year in the United States, and on average 333,000 cases in developing countries. The case fatality rate ranges between 10 and 20 per cent.[2]. While Meningococcal disease is not as contagious as the common cold (which is spread through casual contact), it can be transmitted through saliva and occasionally through close, prolonged general contact with an infected person. 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 including stiff neck, fever and rashes. The meninges (and sometimes the brain itself) begin to swell, which affects the central nervous system. 1 in 10 victims of meningococcal meningitis will die, however survivors of the disease are often left deaf or with 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, patient's health can change from seemingly good to mortally ill.[3]. 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 suffering from 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[4]. Types of infection Septicemia Meningococcal septicemia, like many gram-negative blood infections, can cause disseminated intravascular coagulation (DIC), a condition where blood starts to clot throughout the body, sometimes causing ischemic tissue damage. DIC also causes bleeding, when the clotting factors are used up, causing the characteristic purpuric rash. Meningitis Meningococcal meningitis is a consequence of bacteria entering the cerebrospinal fluid (CSF) and irritating the meninges - the membranes that line the brain and spinal cord. Sub-Saharan Africa, Americas, Western Europe, UK and Ireland face multifarious challenges, 200 years after the discovery of bacterial meningitis[5]. Other types As with any gram negative bacterium, N. meningitidis can infect a variety of sites. Meningococcal pneumonia can appear during influenza pandemics and in military camps. This is a multilobar, rapidly evolving pneumonia, sometimes associated with septic shock. With prompt treatment with penicillin or chloramphenicol, the prognosis is excellent. Pericarditis can appear, either as a septic pericarditis with grave prognosis or as a rective pericarditis in the wake of meningitis or septicaemia. Myocarditis can be a complication of meningococcemia and can be contributive to shock seen in this form of disease. Pharyngitis and conjunctivitis can also appear and can constitute the portal of entry for the bacterium. Septic arthritis due to N. meningitidis can be seen, usually accompanying disseminated infection. Other forms of disease can rarely be seen, like osteomyelitis, endophthalmitis and urethritis. Prevention The most important form of prevention is a Meningococcal vaccine against N. meningitidis. Different countries have different strains of the bacteria and therefore use different vaccines. Five serogroups, A, B, C, Y and W135 are responsible for virtually all cases of the disease in humans. Vaccines are currently available against four of the five strains, and a vaccine against the B strain is in development. Menactra, Menomune of Sanofi-Aventis, Mencevax of GlaxoSmithKline and NmVac4-A/C/Y/W-135 (has not been licensed in the US) of JN-International Medical Corporation are the commonly used vaccines. Unfortunately, there is currently no evidence that any of the current vaccines offer significant protection beyond 18 months (plain polysaccharide vaccine Menomune, Mencevax and NmVac-4) to three years (polysaccharide protein conjugate vaccine Menactra, NmVac4-A/C/Y/W-135 - DT.[13][14] 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. Safety and efficacy of Meningitis A,C,Y and W-135 vaccines have not been established in children younger than 11 years of age; however, clinical studies in children 2–10 years of age have been recommended [15].[16][17].[18]. Children and adolescents 11 years of age or older: It is recommend that primary immunization against meningococcal disease with Meningitis A,C,Y and W-135 vaccines for all young adolescents at 11–12 years of age and all unvaccinated older adolescents at 15 years of age. Although Meningitis A,C,Y and W-135 vaccines are the preferred meningococcal vaccine in adolescents 11 years of age or older, Meningitis A,C,Y and W-135 vaccines are an acceptable alternative if the conjugated vaccine is unavailable.[16][17][19][20] Adults: College Students who plan to live in dormitories receive primary immunization with Meningitis A,C,Y and W-135 vaccines. Although the risk for meningococcal disease for is similar to 18–24 years of age that for the general population of similar age. The college students consider vaccination against meningococcal disease to reduce their risk for the disease and stated that college health-care providers should take a proactive role in providing information about meningococcal disease to students and their parents.[21] Routine primary immunization against meningococcal disease is recommended for most adults live in endemic areas and planning to travel such areas. Although Meningitis A,C,Y and W-135 vaccines are the preferred meningococcal vaccine in adults 55 years of age or younger, Meningitis A,C,Y and W-135 vaccines are an acceptable alternative for adults in this age group if the conjugated vaccine is unavailable. Since safety and efficacy of Meningitis A,C,Y and W-135 vaccines in adults older than 55 years of age have not been established to date, Meningitis A,C,Y and W-135 vaccines should be used for primary immunization in this group.[16][17] Medical staff and laboratory personnel: 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 rifampin or a single dose of IM ceftriaxone or a single dose of oral ciprofloxacin).[16][22] Military recruits: Because the risk of meningococcal disease is increased among military recruits, all military recruits routinely receive primary immunization against the disease.[23] Travelers and tourists: Immunization against meningococcal disease is not a requirement for entry into any country, unlike Yellow fever. Only Saudi Arabia require that travelers to their 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.[17][24] 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.[22] 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.[22] Vaccination against meningitis do 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.[25][26][27] Household and other close contacts of individuals with invasive 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. Unlike, developed countries, in sub-Saharan Africa and other under developed countries, entire family live in a single room of a house.[28][29] 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.[30] By preventing susceptible contacts from acquiring infection by directly inhibiting colonization. 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.[31] 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. Vaccinations are the only answer for reducing the transmission of the Meningococcal disease.[32][33]
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