Meningococcal meningitis (MM) is a serious form of bacterial infection resulting in inflammation of meninges.
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.
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:
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.
Cartwright K, Reilly S, White D, Stuart J. Early treatment with parenteral penicillin in meningococcal disease. BMJ. 1992; 305(6846):143-147.