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Meningococcal Meningitis
Inflammation of the Meninges due to Meningococci

Meningococcal meningitis (MM) is a serious form of bacterial infection resulting in inflammation of meninges.

Presentation

N. meningitidis mainly affects the central nervous system and often starts with respiratory illness. Major symptoms of MM include acute severe headache, fever, photophobia, drowsiness, stiff neck, nausea and vomiting.  Distorted mental state and persistent fever are often seen in older patients. Patients entering coma state is less frequent and in such condition the recovery will be poor. Presences of skin rashes indicate progression of MM.  

MM often results in fulminant meningococcemia syndromes manifested as sepsis with multiple organ dysfunction, disseminated intravascular coagulation, shock and Waterhouse-Friderichsen syndrome presented in the form of septicemia, cutaneous purpura and adrenal hemorrhage. Recurrent mild symptoms are observed in case of a rare chronic MM. The mortality rate of confirmed cases of MM is approximately 5% to 10% (24 to 48 hours post clinical presentation) despite early diagnosis and prompt treatment. About 10 to 20% of convalescing patients sustain brain injury, loss of hearing or a cognitive disability. Meningococcal septicaemia, a fatal form of MM with haemorrhagic rashes and rapid circulatory collapse is less common.

Young children have a different pattern of clinical manifestation and the classic symptoms of MM may not be present[8]. Infants have subtle onset and stiff neck is usually not present. Patients usually exhibit a subacute infection pattern which then progresses over multiple days. Projectile vomiting is often observed. About 40% of them develop focal onset seizures during the initial stages. 

Entire Body System

  • Fever

    Essentials of Diagnosis Fever, headache, vomiting, delirium, convulsions Petechial rash on skin and mucous membranes Neck and back stiffness Purulent spinal fluid with gram-negative intracellular and extracellular diplococci Culture of cerebrospinal fluid [accessmedicine.mhmedical.com]

    Questions will focus on symptoms and possible exposure to someone who might have the same symptoms, such as a stiff neck and fever. [mountsinai.org]

    Since the incidence of most types of meningitis is highest among this age group, any unexplained fever needs to be closely watched. [rarediseases.org]

    (inanition) (of unknown origin) (persistent) (with chills) (with rigor) R50.9 ICD-10-CM Diagnosis Code R50.9 Fever, unspecified 2016 2017 2018 2019 Billable/Specific Code Applicable To Fever NOS Fever of unknown origin [FUO] Fever with chills Fever with [icd10data.com]

    Read more ‘In the space of 5 hours she’d gone from a headache and fever, to nothing they could do.’ [health.govt.nz]

  • High Fever

    This includes a high fever, weakness, or signs of an allergic reaction, such as trouble breathing, a fast heartbeat, or dizziness. [webmd.com]

    Clinical Presentation The most common clinical presentation of meningococcal infection is acute meningitis, characterized by sudden onset of high fever, intense headache, and stiff neck. [menafrinet.org]

    The most common symptoms are a stiff neck, high fever, sensitivity to light, confusion, headaches and vomiting. [africacdc.org]

    Symptoms Anyone experiencing high fever with a new skin rash or other symptoms of meningitis, such as headache or stiff neck, should be examined by a healthcare provider immediately. [health.ri.gov]

    The signs and symptoms of meningitis include high fever, neck pain and stiffness, severe headache, mental status changes (confusion, lethargy), vomiting, and/or rash. The initial symptoms can resemble the flu. [uhs.berkeley.edu]

  • Chills

    Early symptoms are flu-like and include: Fever Chills Weakness Muscle aches These symptoms can progress quickly over the next day or so to include: Headache Stiff neck Widespread rash Vomiting Loss of consciousness People who experience these symptoms [nyc.gov]

    […] bottle cries when picked up or being held inconsolable crying bulging fontanelle (soft spot on an infants head) behavior changes In children older than one year neck and/or back pain headache nausea and vomiting neck stiffness For meningococcemia fever chills [childrenshospital.org]

    Signs and symptoms of meningococcal disease Meningococcal meningitis Meningococcemia Children >1 year and adults Neck stiffness Headache Nausea and vomiting Neck and/or back pain Fever and chills Increased sensitivity to light Irritability, confusion [dermnetnz.org]

    (with rigor) R50.9 ICD-10-CM Diagnosis Code R50.9 Fever, unspecified 2016 2017 2018 2019 Billable/Specific Code Applicable To Fever NOS Fever of unknown origin [FUO] Fever with chills Fever with rigors Hyperpyrexia NOS Persistent fever Pyrexia NOS spotted [icd10data.com]

    Symptoms Symptoms usually come on quickly, and may include: Fever and chills Nausea and vomiting Purple, bruise-like areas (purpura) Severe headache Stiff neck Other symptoms that can occur with this disease: Agitation Bulging fontanelles in infants Decreased [mountsinai.org]

  • Malaise

    Meningococcal meningitis typically starts like the flu, with the sudden onset of an intense headache, fever, sore throat, nausea, vomiting, and malaise. [medicinenet.com]

    Signs and symptoms Fever Headache Loss of appetite Neck stiffness Discomfort when looking at bright lights Nausea and/or vomiting Diarrhea Aching or sore muscles Difficulty walking General malaise Moaning, unintelligible speech Drowsiness Confusion Collapse [safety.colostate.edu]

    • Meningococcemia presents abruptly with fever, chills, nausea, vomiting, headache, myalgias, malaise, prostration, and rash. [medlink.com]

    Incubation period The average incubation period is 4 days, ranging between 2 and 10 days Signs and Symptoms High fever Severe headache, Vomiting or Nausea with Headache Generalised malaise, Confusion Seizures Sleepiness or Difficulty waking up Stiff neck [kznhealth.gov.za]

  • Recent Upper Respiratory Infection

    Risk factors include recent exposure to someone with meningococcal meningitis and a recent upper respiratory infection. [ufhealth.org]

    upper respiratory infection. 17, 19 Approximately 70 to 80 percent of the serogroups most likely to cause meningococcal disease in adolescents and young adults are potentially preventable by the tetravalent meningococcal vaccine. [aafp.org]

Gastrointestinal

  • Vomiting

    The symptoms are similar to bacterial meningitis: fever, stiff neck, headache, nausea and vomiting, light sensitivity. The symptoms are often less severe than bacterial meningococcal illnesses. [safety.colostate.edu]

    Symptoms of meningitis include sudden onset of fever, headache, stiff neck, nausea, vomiting, sensitivity to light, and confusion. [doh.wa.gov]

    Disease definition Meningococcal meningitis is an acute bacterial disease caused by Neisseria meningitides that presents usually, but not always, with a rash (non blanching petechial or purpuric rash), progressively developing signs of meningitis (fever, vomiting [orpha.net]

    Nausea, vomiting, light sensitivity, confusion, and rash. Symptoms can differ in infants and may include: Slow or inactivity, irritability, vomiting, poor feeding, or a bulging soft spot on their head. [floridahealth.gov]

    Herein we report an 11-year-old-Syrian refugee girl living in Turkey for 3 months admitting with fever, headache, and vomiting diagnosed as meningococcal meningitis type B who was cured with intravenous ceftriaxone therapy. [ncbi.nlm.nih.gov]

  • Nausea

    The symptoms are similar to bacterial meningitis: fever, stiff neck, headache, nausea and vomiting, light sensitivity. The symptoms are often less severe than bacterial meningococcal illnesses. [safety.colostate.edu]

    Symptoms may include sudden onset of fever, headache, rash, limb pain, stiff neck, nausea, vomiting, photophobia (eyes being more sensitive to light), and altered mental status (confusion). [cdph.ca.gov]

    Signs and Symptoms Fever Intense headache Nausea Vomiting Neck stiffness Petechial or purpuric rash on the trunk and limbs Can lead to sepsis, pneumonia and death. [deputyprimeminister.gov.mt]

    Meningococcal meningitis typically starts like the flu, with the sudden onset of an intense headache, fever, sore throat, nausea, vomiting, and malaise. [medicinenet.com]

Cardiovascular

  • Tachycardia

    Factors associated with mortality in the multivariate model were age above 50 years, seizures, tachycardia, hypotension and neck stiffness. The classic clinical and laboratory triads of meningococcal meningitis were variable. [ncbi.nlm.nih.gov]

    Shock signs (i.e. hypotension, tachycardia) are classically associated with higher mortality in patients with acute bacterial meningitis 3, 12, 18, 27, 28. [scielo.br]

    Tachycardia and/or hypotension; respiratory symptoms or breathing difficulty. Leg pain. Poor urine output. [patient.info]

Skin

  • Petechiae

    We underline that when a patient presents fever and petechiae (50-60% of patients), WFS must be considered, even when the patient has a non-toxic appearance. [ncbi.nlm.nih.gov]

    […] dominate the picture In severe cases, rapidly developing confusion, delirium, seizures, and coma occur Nuchal and back rigidity are typical A petechial rash often first appearing in the lower extremities and at pressure points is found in most cases Petechiae [accessmedicine.mhmedical.com]

    Bleeding into the skin (petechiae and purpura) usually occurs and the tissue may die (become necrotic or gangrenous). If the patient survives, the areas heal with scarring. The central nervous system comprises the brain and spinal cord. [mountsinai.org]

    General poor feeling Sudden high fever Severe, persistent headache Neck stiffness Nausea or vomiting Discomfort in bright lights Drowsiness or difficulty awakening Joint pain Confusion or other mental changes A reddish or purple skin rash (known as petechiae [webmd.com]

    See also Meningitis Sepsis Fever and petechiae/purpura Key Points IV ceftriaxone / cefotaxime should be given as soon as meningococcal disease is suspected. If unavailable, give penicillin. [rch.org.au]

Musculoskeletal

  • Neck Pain

    See also[edit] Neck pain Acquired torticollis References[edit] ^ "Neck pain". MedlinePlus. National Institutes of Health. 5 March 2015. Retrieved 27 October 2015. ^ "Neck pain and stiff neck". NHS Choices. National Health Service. 10 December 2014. [en.wikipedia.org]

    The signs and symptoms of meningitis include high fever, neck pain and stiffness, severe headache, mental status changes (confusion, lethargy), vomiting, and/or rash. The initial symptoms can resemble the flu. [uhs.berkeley.edu]

    Other symptoms include: severe headache, vomiting, stiff neck, pain when moving the head or neck, aches and pains, joint pain, and seizures. [caringforkids.cps.ca]

Eyes

  • Photophobia

    Neck stiffness and photophobia are often absent in infants and young children who may manifest nonspecific signs such as irritability, inconsolable crying, poor feeding, and a bulging fontanel. [orpha.net]

    Symptoms may include sudden onset of fever, headache, rash, limb pain, stiff neck, nausea, vomiting, photophobia (eyes being more sensitive to light), and altered mental status (confusion). [cdph.ca.gov]

    Major symptoms of MM include acute severe headache, fever, photophobia, drowsiness, stiff neck, nausea and vomiting. Distorted mental state and persistent fever are often seen in older patients. [symptoma.com]

    The Illness Symptoms of meningitis usually include one or more of the following; Sudden onset of fever Intense headache Nausea Vomiting Photophobia (intolerance of light) Stiff neck Petechial rash (blood spots under the skin) If one or more of the symptoms [fitfortravel.nhs.uk]

    These often come with by nausea, vomiting, an increased sensitivity to light (called photophobia), or a change in mental status. Symptoms can come on quickly or over several days. Typically they develop within three to seven days after exposure. [apic.org]

Neurologic

  • Headache

    So in the space of 5 hours, she’d gone from a headache and fever to nothing they can do. The only real symptoms was the headaches, the temperature, the vomiting and that was pretty much it. [health.govt.nz]

    The symptoms are similar to bacterial meningitis: fever, stiff neck, headache, nausea and vomiting, light sensitivity. The symptoms are often less severe than bacterial meningococcal illnesses. [safety.colostate.edu]

    Clinical manifestations include FEVER, nuchal rigidity, SEIZURES, severe HEADACHE, petechial rash, stupor, focal neurologic deficits, HYDROCEPHALUS, and COMA. [connects.catalyst.harvard.edu]

    […] definition Meningococcal meningitis is an acute bacterial disease caused by Neisseria meningitides that presents usually, but not always, with a rash (non blanching petechial or purpuric rash), progressively developing signs of meningitis (fever, vomiting, headache [orpha.net]

    […] nausea and vomiting neck stiffness For meningococcemia fever chills sore throat headache aching muscles and joints exhaustion and weariness rash, which may appear small, red flat or raised, fine at first and then changes to larger red patches or purple [childrenshospital.org]

  • Confusion

    […] caused by Neisseria meningitides that presents usually, but not always, with a rash (non blanching petechial or purpuric rash), progressively developing signs of meningitis (fever, vomiting, headache, photophobia, and neck stiffness) and later leading to confusion [orpha.net]

    Symptoms may include sudden onset of fever, headache, rash, limb pain, stiff neck, nausea, vomiting, photophobia (eyes being more sensitive to light), and altered mental status (confusion). [cdph.ca.gov]

    The most common symptoms are a stiff neck, high fever, sensitivity to light, confusion, headaches and vomiting. [africacdc.org]

    Disoriented; impaired thinking and responses People who do not respond quickly with information about their name, location, and the time are considered "obtuse" or "confused".[8] A confused person may be bewildered, disoriented, and have difficulty following [en.wikipedia.org]

    Signs and symptoms Fever Headache Loss of appetite Neck stiffness Discomfort when looking at bright lights Nausea and/or vomiting Diarrhea Aching or sore muscles Difficulty walking General malaise Moaning, unintelligible speech Drowsiness Confusion Collapse [safety.colostate.edu]

  • Seizure

    Age, seizures and shock signs were independently associated with mortality. [ncbi.nlm.nih.gov]

    Clinical manifestations include FEVER, nuchal rigidity, SEIZURES, severe HEADACHE, petechial rash, stupor, focal neurologic deficits, HYDROCEPHALUS, and COMA. [connects.catalyst.harvard.edu]

    Surviving patients may develop neurological sequelae that include sensorineural hearing loss, seizures, spasticity, attention deficits and intellectual disability. [orpha.net]

    If not treated early, the disease can lead to swelling of the fluid surrounding the brain and spinal column as well as severe and permanent disabilities, such as hearing loss, brain damage, seizures, limb amputation, and even death. [healthservices.appstate.edu]

    Early complications of bacterial meningitis include seizures, raised intracranial pressure (seen in the image below), cerebral venous thrombosis, sagittal sinus thrombosis, and hydrocephalus. [emedicine.medscape.com]

  • Irritability

    Neck stiffness and photophobia are often absent in infants and young children who may manifest nonspecific signs such as irritability, inconsolable crying, poor feeding, and a bulging fontanel. [orpha.net]

    […] quickly, and may include: Fever and chills Nausea and vomiting Purple, bruise-like areas (purpura) Severe headache Stiff neck Other symptoms that can occur with this disease: Agitation Bulging fontanelles in infants Decreased consciousness Poor feeding or irritability [mountsinai.org]

    All except one presented with signs and symptoms suggestive of meningeal irritation; all but one responded to intravenous quinine and chloramphenicol or ampicillin. [ncbi.nlm.nih.gov]

    […] come on quickly, and may include: Nausea and vomiting Purple, bruise-like areas ( purpura ) Severe headache Stiff neck Other symptoms that can occur with this disease: Agitation Bulging fontanelles in infants Decreased consciousness Poor feeding or irritability [ufhealth.org]

  • Neck Stiffness

    Neck stiffness and photophobia are often absent in infants and young children who may manifest nonspecific signs such as irritability, inconsolable crying, poor feeding, and a bulging fontanel. [orpha.net]

    The clinical triad: fever, headache and neck stiffness was observed in 89% of the patients. The cerebrospinal triad: pleocytosis, elevated protein levels and low glucose levels was present in 79% of patients. [ncbi.nlm.nih.gov]

    Neck stiffness, Texas meningitis epidemic of 1911–12 Neck stiffness, stiff neck and nuchal rigidity are terms often used interchangeably to describe the medical condition when one experiences discomfort or pain when trying to turn, move, or flex the neck [en.wikipedia.org]

    Signs and Symptoms Fever Intense headache Nausea Vomiting Neck stiffness Petechial or purpuric rash on the trunk and limbs Can lead to sepsis, pneumonia and death. [deputyprimeminister.gov.mt]

Workup

Clinical symptoms of the patient upon admission and preliminary examination of cerebrospinal fluid (CSF) helps in diagnosis. Serological analysis of blood (e.g. coagglutination tests and latex agglutination), CSF, urine and synovial fluid helps in timely tentative detection of MM. However these results are to be confirmed with further micorbiological culture tests and microscopic analysis specific for the pathogen. Detection of microbes in CSF via microscopy (Gram staining) or culture methods confirms and aids in identifying of causative organism. Among untreated cases the detection rate via Gram staining and culture techniques is around 70-90% and 80% respectively.

The culture technique may fail if the patient is on antibiotic treatment [9] or when the microbes are fastidious and slow growing. Molecular diagnostic methods like polymerase chain reaction (PCR) help in diagnosis under such conditions [10] [11]. However it has to be noted that PCR for N. meningitidis is not commercially available despite being developed. Detection of intracranial hypertension, intracerebral hemorrhage and edema via head CT scan also indicates infection. The identification of the serotype responsible for infection and antibiogram analysis should be performed to decide the appropriate antibiotic treatment.

Treatment

Treatment of immunocompetent patients is started right away in suspected cases of MM using dexamethasone (corticosteroid), vancomycin and third-generation cephalosporins like ceftriaxone and cefotaxime). Corticosteroids are given with or prior to antibiotic therapy to reduce the occurrence of neurologic complications. In immunocompromised patients and patients over 50 years, ampicillin is prescribed as a cover to possible Listeria monocytogenes infection. In accordance to the initial CSF results, administration of acyclovir is considered. Doxycycline is used in tick seasons in endemic regions. Uncomplicated meningococcal meningitis is managed via intravenous ceftriaxone or penicillin course for 7 consecutive days.

Lumbar puncture for retrieving CSF is done prior to antibiotic treatment owning to the inability of microscopic and culture techniques to detect Nm in patients undergoing antibiotic therapy. Third-generation cephalosporins like ceftriaxone or cefotaxime is prescribed for managing meningitis and septicemia once MM is confirmed. Owning to the highly contagious nature of MM, close contacts of confirmed cases are given antibiotics as prophylactic measure within 24 hours of confirmation of MM in index patient [3]. Under epidemic situations in regions with limited financial and health care infrastructure, ceftriaxone is used to manage the situation.

Prognosis

The prognosis is fair in absence of focal neurological deficits and coma. The prognosis has a poor outcome when the infection is septicemic. Most MM patients convalesce completely under prompt antibiotic treatment. Poor prognostic factors include low blood platelet count, low coagulation index, moderate anemia with hemoglobin less than 11 g/dL, altered mental status and history of convulsions. Meningococcal disease is a medical emergency condition requiring immediate treatment. Timely antibiotic treatment is required when MM is suspected in order to arrest severe neurologic morbidity and death. Morbidity and mortality are high for meningococcal infection in pediatric patients.

Etiology

MM (International Classification of Disease-9 (ICD-9) code: 036.0) is considered as a major crisis for the past two centuries. Neisseria meningitidis, gram-negative diplococci is the major causative organism of MM which is capable of initiating large epidemics. Out of the 12 serogroups of Nm, 6 serogropus (A, B, C, W, X and Y) have the potential to cause epidemics. 

Individuals lacking protective bactericidal antibodies contract MM upon exposure to the virulent bacteria. Human nasopharyngeal mucous membranes and, to a minor extent, the genitourinary tract and anal canal serves as the reservoir and natural habitat for N. meningitidis. MM is an airborne infection spreading through aerosol droplets or via contact with respiratory secretions by kissing, sharing drinking and eating utensils, mouth-to-mouth breathing for resuscitation or by intubation [1]. It is estimated that less than 2% of children [2] and 5-10% of adult population are asymptomatic nasopharyngeal carriers of N. meningitidis. The percentage of carriers increases to as much as 60-80% in closed populations like military camps and dormitories. Young children under two years are at greater risk of contracting MM [3] and can result in severe brain damage and if left untreated, can be mortal in 50% of cases.

Epidemiology

N. meningitidis (serogroup B) is the major causative agent in Europe and America. Formerly serogroup A was responsible for global epidemics but now it is reported only in African and Asian epidemics. An increase in incidence of epidemics initiated by serogroup B and Y has been observed since 1990. From 1991 an increase in the rate of recurrence of localized outbreaks has been observed [4] [5]. The annual incidence of MM in general population is 1–5 /105 people [6]. The disease is highly fatal with high morbidity and mortality despite high level of awareness and timely medical attention. Minor outbreaks are observed when people live in close quarters however the risk of contracting MM decreases with age. Approximately 1.2 million cases of invasive meningococcal disease (IMD) are reported annually with 135000 deaths [7].

Pathophysiology

N. meningitidis specifically infect humans and does not have any animal reservoir. MM is an airborne disease contracted through respiratory droplets from the respiratory tract of the asymptomatic carriers. The infection has a latent period of 3-4 which can extend up to 10 days during which the patient is highly infective. Nm can be observed for about 2 to 4 days in the upper respiratory tract (URT) and it lingers there upto 24 hours post antibiotic therapy. Once menengococci come in contact with the nasopharyngeal mucosa, it adheres to it and is subsequently engulfed by the membrane bound phagocytic vacuoles. They can be observed in submucosa, near blood vessels and local immune system cells 24 hours post infection. In most of the cases, infection will only be subclinical or with milder manifestations. Infections get complicated when Nm invade the submucosa. MM may then progress to more fatal meningococcemia 24-48 hours post infection in around 10-20% of cases. Nm results in severe bacteremia with intense vascular effects and can quickly become fulminant. The mortality rate is approximately 10 to 15% and about 10 to 15% of those who recover from MM suffer severe after effects like permanent hearing loss, cognitive impairment or phalanges or limb loss. Asymptomatic carriers rarely become symptomatic and infection is mainly reported in previously uninfected people. Penicillin in found to be generally ineffective for treating nasopharyngeal carriers.

Prevention

Immunoprophylatic and chemoprophylactic methods are used to prevent MM . Antibiotics like quinolones, ceftriaxone and rifampicin is found to be effective in preventing the spread of disease through asymptomatic carriers. Vaccines against Nm serogroup A, C, Y, or W135 are available for protecting close contacts of invasive MM patients from contracting the disease [12]. Antibiotics like rifampicin, ceftriaxone and fluoroquinolone (ciprofloxacin, levofloxacin or ofloxacin) are also given to them as a prophylactic measure.

The risk factors for developing MM include smoking and concomitant viral infection of the URT which weaken the ability of mucous membrane to effectively ward off the invasive bacterial pathogens. Over crowded living arrangements often result in outbreaks as individuals from different areas carry different strains and have different levels of immunity.

Several meningococcal conjugate vaccines available in the US include: 

  • MenACWY-D - 2 quadrivalent conjugate vaccines that confers protectect against 4 common serogroups of meningococcus
  • Hib-MenCY - A bivalent conjugate vaccine acting against serogroup C and Y. It is available only as a combination with Haemophilus influenzae type b vaccine
  • MenACWY-CRM - A quadrivalent polysaccharide vaccine for patients over 56 years of age.

Summary

Meningococcal meningitis (MM) is an acute, airborne bacterial infection caused by Neisseria meningitides (Nm). Inflammation of meninges (membranes covering the brain and spinal cord) is the major complication. The initial symptoms of MM include the development of purpuric or petechial non blanching rash which is subsequently followed by fever, vomiting, photophobia, headache and stiff neck. Confusion, delirium and drowsiness follows shortly afterwards. Infants and young children does not manifest neck stiffness and photophobia. They exhibit non specific symptoms like inconsolable crying, poor feeding, irritability and bulging fontanelle. MM is potentially fatal and in some instance is manifested as an early or late symptom of sepsis in neonates.

Patient Information

Bacteria causing meningitis spread among individuals through direct contact of respiratory discharges via kissing, sharing drinking glasses etc. There is an increase risk of contracting the disease if you live in crowded condition. Meningococcal disease is a fatal infection and may result in death if left untreated or delayed. Early medical attention with appropriate antibiotics therapy improves the condition significantly. Recommended vaccination should be done in order to stay protected against MM. In case of suspected MM, all immediate close contacts must get a course of antibiotic as chemoprophylactic measure to arrest the spread of infection and carrier state [13]. Rifampin, ciprofloxacin, or ceftriaxone are the antibiotics given as chemoprophylactic agent to close contacts of index patient. 

The risk of death is highest for young children and patients above 50 years of age. MM can quickly progress to complications and fatality or may result in serious neurologic and vascular after effects even after antibiotic therapy. Most of the MM cases reported as sporadic however effective active vaccination is important to prevent outbreaks within the affected population.

References

  1. Granoff DM, Feavers IM, Borrow R. Meningococcal vaccines. In: Plotkin SA, Orenstein WA, eds. Vaccines. 4th ed. Philadelphia: Saunders, 2004:959-987.
  2. Schaffner W, Harrison LH, Kaplan SL, Miller E, Orenstein W, Peter G, Rosenstein N. The changing epidemiology of meningococcal disease among U.S. children, adolescents and young adults. National Foundation for Infectious Diseases (pamphlet). 2004:1–15.
  3. Bilukha OO, Rosenstein N. Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practice. MMWR Recomm Rep. 2005;54:(RR-7)1-21.
  4. Jackson LA, Schuchat A, Reeves MW, Wenger JD. Serogroup C meningococcal outbreaks in the United States. An emerging threat. JAMA. 1995;273(5):383-389.
  5. Ahlawat S, Kumar R, Roy P, Varma S, Sharma BK. Meningococcal meningitis outbreak control strategies. J Commun Dis. 2000;32(4):264-274.
  6. Warrell DA, Farrar JJ, Crook DWM. Bacterial meningitis. In: Warrell DA, Cox TM, Benz EJ, eds. Oxford textbook of medicine. 4th ed. Oxford: Oxford University Press, 2003.
  7. Epidemics of meningococcal disease. African meningitis belt, 2001. Wkly Epidemiol Rec. 2001; 76(37):282-288.
  8. Chin RF, Neville BG, Scott RC. Meningitis is a common cause of convulsive status epilepticus with fever. Arch Dis Child. 2005; 90(1):66-69.
  9. Cartwright K, Reilly S, White D, Stuart J. Early treatment with parenteral penicillin in meningococcal disease. BMJ. 1992; 305(6846):143-147.

  10. Kotilainen P, Jalava J, Meurman O, et al. Diagnosis of meningococcal meningitis by broad-range bacterial PCR with cerebrospinal fluid. J Clin Microbiol. 1998; 36(8):2205-2209.
  11. Pardo F, Juncal R, Rajo C, Perez del Molino ML. Usefulness of polymerase chain reaction (PCR) in the diagnosis of meningococcal meningitis]. Enferm Infecc Microbiol Clin. 1999; 17(2):74-77.
  12. Shao PL, Chang LY, Hsieh SM, Chang SC, Pan SC, Lu CY, et al. Safety and immunogenicity of a tetravalent polysaccharide vaccine against meningococcal disease. J Formos Med Assoc. 2009; 108(7):539-547.
  13. Cuevas LE, Hart CA. Chemoprophylaxis of bacterial meningitis. J Antimicrob Chemother. 1993; 31 Suppl B:79-91.
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