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. 

• Fever

  (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]

  Although less than one third of affected patients present with the classic triad of fever, nuchal rigidity, and change in mental status, nearly 90% have at least 2 of the following 4 signs on presentation: fever, nuchal rigidity, change in mental status [medlink.com]

  Abstract We describe a rare case of infantile meningococcal (serotype B) meningitis in a 3-month-old Chinese boy with an atypical indolent presentation with prolonged persistent fever despite appropriate antimicrobial therapy likely due to drug fever. [ncbi.nlm.nih.gov]

  […] and the National Institute for Health and Care Excellence (NICE) fever guidelines, and highlighting the need for sustained vigilance for bacterial infections in infants with post-4CMenB fever. [adc.bmj.com]

• High Fever

  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]

  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]

  […] headaches Limb, joint & muscle pain Vomiting Stiff neck Symptoms in Infants: Some of the symptoms most commonly associated with meningitis, such as high fever, stiff neck or headache might not appear or might be difficult to detect in babies or infants [nmaus.org]

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

• 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 rigors Hyperpyrexia NOS Persistent fever Pyrexia NOS spotted [icd10data.com]

  Patients who present with meningococcal septicemia could have many symptoms, including: High fever Fatigue Vomiting or diarrhea Cold hands and feet Cold chills Severe aches or pain in the muscles, joints, chest, or abdomen (belly) Rapid breathing Purpuric [menafrinet.org]

  Some individuals may have other reactions like headache, fever and chills. If you have a healthcare plan, an HMO or PPO health insurance plan, you may want to contact your provider. [winthrop.edu]

  Some common symptoms include: Fever and chills Feeling tired Throwing up and diarrhea (watery poop) Cold hands and feet Severe aches or pain in the muscles, joints, chest, or stomach As many as 1 in 5 people who survive meningococcal disease will have [vaccines.gov]

• 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]

  Your risk also increases if you've had a recent upper respiratory infection. Babies, children, and teens are at greatest risk. What Are the Symptoms of Meningococcal Meningitis? Symptoms of meningococcal meningitis may vary from case to case. [webmd.com]

• 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]

  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]

  There are often additional symptoms, such as: Nausea Vomiting Photophobia (increased sensitivity to light) Altered mental status (confusion) These symptoms can develop within several hours or may develop 3 to 7 days after exposure. [menafrinet.org]

  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]

• 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]

  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 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]

  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]

• 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]

• 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]

  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]

  An aspirate (material drawn in negative pressure from a syringe) from petechiae and meningococci can also be cultured from CSF or blood and detected by PCR (polymerase chain reaction). [myvmc.com]

  Symptoms usually come on quickly, and may include: Fever and chills Mental status changes Nausea and vomiting Purple, bruise-like areas ( purpura ) Rash, pinpoint red spots ( petechiae ) Sensitivity to light ( photophobia ) Severe headache Stiff neck [medlineplus.gov]

  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 is comprised of the brain and spinal cord. [mountsinai.org]

• Neck Pain

  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]

• Photophobia

  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]

  There are often additional symptoms, such as: Nausea Vomiting Photophobia (increased sensitivity to light) Altered mental status (confusion) These symptoms can develop within several hours or may develop 3 to 7 days after exposure. [menafrinet.org]

  Photophobia*. Bulging fontanelle. Late features Confusion* or delirium. Seizures. Unconsciousness. [patient.info]

  The most common symptoms include: Fever Headache Stiff neck There are often additional symptoms, such as Nausea Vomiting Photophobia (eyes being more sensitive to light) Altered mental status (confusion) Newborns and babies may not have or it may be difficult [cdc.gov]

• Headache

  A 44-year-old man with a history of presumed meningococcal meningitis 32 years before, presented with a three-month illness, characterized by fever, 13.5-kg (30-lb) weight loss, occipital headache, shoulder pain, and muscle weakness, which had been diagnosed [ncbi.nlm.nih.gov]

  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]

• Confusion

  Its symptoms also include confusion, or irritability in infants, and a stiff neck. You should see your doctor right away if you suspect that you or a loved one might have meningococcal meningitis. [healthline.com]

  Rash, stiff neck, high fever, sensitivity to light, confusion, headaches and vomiting. 1 How serious is the disease? Meningitis caused by bacteria can be fatal if it’s not treated quickly. [bewareofthebugs.com]

  The most common symptoms include high fever, headaches, neck stiffness, confusion, nausea, vomiting, lethargy and/or rashes. Anyone with similar symptoms should contact a physician immediately. [web.csulb.edu]

  There are often additional symptoms, such as: Nausea Vomiting Photophobia (increased sensitivity to light) Altered mental status (confusion) These symptoms can develop within several hours or may develop 3 to 7 days after exposure. [menafrinet.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]

• Seizure

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

  The seizure terminated with two doses of intravenous lorazepam and suspected sepsis was treated with immediate intravenous antibiotics. [adc.bmj.com]

  Of those who survive, 10% of the people will have lingering symptoms such as deafness, seizures or stroke. [faculty.washington.edu]

  Seizures in adults with bacterial meningitis. [scielo.br]

  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]

• Irritability

  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]

  […] areas ( purpura ) Rash, pinpoint red spots ( petechiae ) Sensitivity to light ( photophobia ) Severe headache Stiff neck Other symptoms that can occur with this disease: Agitation Bulging fontanelles in infants Decreased consciousness Poor feeding or irritability [medlineplus.gov]

  […] 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]

• Neck Stiffness

  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]

  Meningococcal meningitis may be indistinguishable from other bacterial meningitides, although the classic triad of fever, neck stiffness, and change in mental status is significantly less common in patients with meningococcal meningitis (27%) than in [medlink.com]

  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]

  The most common symptoms include high fever, headaches, neck stiffness, confusion, nausea, vomiting, lethargy and/or rashes. Anyone with similar symptoms should contact a physician immediately. [web.csulb.edu]

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 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.

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.

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.

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].

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.

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.

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.

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.

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