Meningococcal Meningitis Dr Saleh H. Al Rowaily Pediatric Consultant General Director Assistant for Curative Services ARAR-Northern Border Region -November 2015

Meningococcal Meningitis Meningitis is the inflammation of the membranes surrounding the brain & spinal cord, including the dura, arachinoid & pia matter

Meningococcal Meningitis Meningococcal meningitis is a bacterial form of meningitis, a serious infection of the thin lining that surrounds the brain and spinal cord The most important pathogen for meningitis is Neisseria meningitides because of its potential to cause epidemics

Problem Statement Occurs worldwide in both endemic and epidemic forms. It is estimated to be responsible for over 500,000 cases and about 135,000 deaths annually ‘African meningitis belt’, stretches across sub – Saharan Africa from Senegal in the west, to Ethiopia in the east. During epidemics this region has a disease incidence rate of >1,000 cases per 10,000 population. The largest recorded outbreak occurred in Africa in 1996 Major epidemics reported from Asia over the past 35 years. China, Vietnam, Mongolia, and Nepal The highest level of meningococcal disease occurs in the ‘African meningitis belt’, which stretches across sub - Saharan Africa from Senegal in the west, to Ethiopia in the east. During epidemics this region has a disease incidence rate of >1,000 cases per 10,000 population. The largest recorded outbreak of meningococcal disease in history occurred in Africa in 1996 where 250,000 cases including 25,000 deaths were reported to the WHO. Major epidemics of menincococcal meningitis have been reported from Asia over the past 35 years. China, Vietnam, Mongolia, Bhutan, and Nepal have all reported large outbreaks with Serogroup B being implicated most often.

Problem Statement Isolated in 1887, N. meningitides is an exclusive human pathogen Natural habitat and reservoir - The mucosal surfaces of the human nasopharynx In most cases colonization of the human nasopharynx is asymptomatic. However, blood stream invasion can lead to meningitis and septicaemia with serious consequences. Even with adequate chemotherapy, meningococcal meningitis has a fatality rate of about 10% and about 15% of the survivors have residual Central Nervous System (CNS) damage

Agent: Neisseria meningitides Bean shaped gram negative, aerobic diplococci. At least 13 serogroups have been described : A, B, C, D, E, H, I, K, L, W - 135, X, Y and Z. Almost all meningococcal infections are caused by five serogroups A, B, C, 29 E or W – 135 Worldwide serogroups A, B and C account for most cases of meningococcal disease The predominant serogroups in Asia and Africa are A & C Recent outbreaks among Haj pilgrims have been attributed to serogroup W – 135 The capsular polysaccharide provides the basis for their classification into serogroups. They differ in their agglutination reactions to sera directed against polysaccharide antigens. Pathogenic meningococci are enveloped by a polysaccharide capsule.

Host and Environment Maternal antibodies offer protection against invasive disease till the age of six months. Susceptibility peaks at age 6 - 12 months and decreases again after colonization of closely related nonpathogenic bacteria. Subsequent colonization with Neisseria Meningitides induces antibodies to the infecting strain, thus reinforcing natural immunity. Invasive disease occurs if no protective bactericidal antibodies are mounted against the infecting strain. Those infected with the Human Immunodeficiency Virus are probably also at increased risk for sporadic meningococcal disease

Host and Environment Highest incidence – 6 months to 2 yrs Rarely reported over 50 years of age. No gender predilection, though males account for slightly more than half the reported cases. Increased Risk with smoking (both active and passive), antecedent upper respiratory tract infection, underlying chronic illnesses are all associated with increased risk of meningococcal disease. Low socioeconomic status - poor housing, overcrowding, and inadequate ventilation consistently associated with higher risk for meningococcal disease The risk of invasive disease is higher in the first few days after exposure to a new strain.

Transmission & Communicability The main modes of transmission are direct contact and respiratory droplets. Close contact like living in close quarters (like military dormitories) and sharing of utensils enhance the risk of transmission The average incubation period is 3 - 4 days with a range of 2 to 10 days. This is also the period of communicability. The bacteria are rapidly eliminated from the nasopharynx after starting antibiotics, usually within 24 hours.

Reservoir Humans are the only reservoir. Both cases and carriers serve as the source of infection. 5 - 10% adults are asymptomatic nasopharyngeal carriers during inter - epidemic periods. This figure can, however, rise to 60 - 80% in closed populations like military recruits in camps

Pathogenic Strain Susceptible Host Colonized on naso - oropharyngeal mucosa Overcome host defense & attach to the microvillous surface of nonciliated columnar mucosal cells of the nasopharynx, mucosal penetration followed by invasion of blood stream and finally, invasion of meninges meningococcemia leading to systemic disease, usually precedes meningitis by 24 to 48 hours Meningococcemia leads to diffuse vascular injury with circulatory collapse and disseminated intravascular coagulation.

Clinical Features Acute onset (within several hrs to 2 days) of intense headache, high fever, nausea, vomiting, photophobia, and stiff neck, altered mental state Less commonly reported symptoms include stupor or coma, which carries a poorer prognosis. A more severe form of disease is meningococcal septicaemia, characterized by a haemorrhagic rash which usually indicates disease progression and rapid circulatory collapse

Clinical Features The symptoms of meningitis vary and depend on the age of the child and cause of the infection. Common symptoms are: Flu-like symptoms fever lethargy Altered consciousness irritability headache photophobia stiff neck Brudzinski sign Kernig sign skin rashes seizures

Clinical Features

Clinical Features Other symptoms of meningitis in Neonates/infants can include: Apnea jaundice neck rigidity Abnormal temperature (hypo/hyperthermia) poor feeding /weak sucking a high-pitched cry bulging fontanelles Poor reflexes

Clinical features In infants and young children there is a slower onset of signs and symptoms with nonspecific symptoms and neck stiffness may be absent. Irritability and projectile vomiting may be the presenting features. Seizures occur in 40% of children with meningitis. The Waterhouse - Friderichsen syndrome may develop in 10 - 20% of children with meningococcal infection, characterized by large petechial haemorrhages in the skin & mucous membranes, fever, septic shock Even when the disease is diagnosed early and adequate therapy instituted, 5% to 10% of patients die, typically within 24 - 48 hours of onset of symptoms. Bacterial meningitis may result in brain damage, hearing loss or learning disability in 10 to 20% of survivors

Clinical features The Waterhouse - Friderichsen syndrome may develop in 10 - 20% of children with meningococcal infection, characterized by large petechial haemorrhages in the skin & mucous membranes, fever, septic shock Death from Waterhouse-Friderichsen

Diagnosis Investigations CBC Blood culture Gram staining LP- D/r, C/s (color, leukocyte count, differential, glucose, protein) Electrolytes PCR Coagulation profile liver and kidney function Chest X-ray CT/ MRI Blood gases EEG ECG

Diagnosis LP

Diagnosis Suspected by the clinical presentation and a L.P. showing a purulent spinal fluid CSF - increased pressure (>180 mm water), WBC counts between10 and 10,000 cells/μL, (predominantly neutrophils), decreased glucose concentration (<45 mg/dL) and increased protein concentration (>45 mg/dL)

Diagnosis Bacteriological diagnosis by Gram staining of CSF, Direct antigen detection using latex agglutination, or Culture- only CSF samples are generally positive. Kits to detect polysaccharide antigen in CSF are rapid and specific and can provide a serogroup - specific diagnosis, but false negatives!

Management Since its potentially fatal, should always be viewed as a medical emergency Early recognition of the disease, prompt initial parenteral antibiotic therapy and close monitoring with frequent repeated prognostic evaluations Several antibiotics can be used for treatment including penicillin, ampicillin, chloramphenicol and ceftriaxone Isolation of the patient is not necessary

A single intramuscular dose of an oily suspension of chloramphenicol has been shown to be as effective as a five - day course of crystalline penicillin in the treatment of meningococcal meningitis. During epidemics, this may offer a practical alternative to penicillin or ceftriaxone which require multiple injections. Antibiotic Adult Dose Pediatric Dose Penicillin 4 million units IV X 4 a day 250,000 Units/Kg/day I.V. in devided doses Ceftriaxone 4 gram IV per day divided into two doses 50 mg/Kg IV divided into two doses (not to exceed 4 g/d).

Prevention and Control Chemoprophylaxis : as soon as possible (ideally within 24 hours), limited or no benefit if given more than 14 days after the onset of disease Adults - Ciprofloxacin single oral dose of 500 mg, Rifampicin 600 mg 12 hourly for two days, or ceftriaxone 250 mg IM single dose Rifampicin should be avoided during pregnancy. Children - rifampicin 10 mg/Kg 12 hourly for two days (5mg/Kg for infants) or injection ceftriaxone 125 mg IM single dose.

Prevention & Control Chemoprophylaxis is not recommended during epidemics because of multiple and prolonged sources of exposure Logistic problems and high cost Secondary cases comprise less than 2% of all meningococcal disease Immunization using safe and effective vaccines is the only rational approach to the control of meningococcal disease.

Prevention & Control Immunization using safe and effective vaccines is the only rational approach to the control of meningococcal disease.

Meningococcal Vaccines Of the five common serotypes responsible for more than 90% of meningococcal disease, vaccines are available for group A, C, Y and W - 135. At present two types of meningococcal vaccines are licensed; meningococcal polysaccharide vaccines (bivalent and quadrivalent) and meningococcal conjugated polysaccharide vaccine.

Polysaccharide Vaccines purified, heat - stable, lyophilized capsular polysachrides Bilvalent- against serogroups A and C, Quadrivalent against serogroups A, C, Y and W - 135. Single dose - of the reconstituted vaccine contains 50 μg of each of the individual polysaccharides. The dose for primary vaccination for both adults and children older than two years is a single 0. 5 - ml subcutaneous injection. The antibody responses to each of the four polysaccharides in the quadrivalent vaccine are serogroup - specific and independent.

Polysaccharide Vaccines purified, heat - stable, lyophilized capsular polysachrides Protective levels of antibody are usually achieved within 7 - 10 days The serogroup A and C vaccines have good immunogenicity, with clinical efficacy rates of 85% to 100% among children five years of age or older and adults. Serogroup Y and W - 135 polysaccharides are safe and immunogenic in older children and adults. Vaccination has been highly effective in the control of community outbreaks and epidemics in military centers. Carrier status is unaffected by vaccination Extremely safe, major drawback is the absence of activity against group B meningococci These unconjugated polysaccharide vaccines confer protection in complement deficient persons also. Vaccination does not reduce the transfer of bacteria to non - vaccinated persons and carrier status is unaffected.

Conjugated polysaccharide vaccine A quadrivalent A, C, Y and W - 135 conjugate vaccine has been licensed since January 2005. Contains 4 μg each of A, C, Y and W - 135 polysaccharide conjugated to 48 μg of diphtheria toxoid. Induce a T - cell - dependent response, resulting in an improved immune response in infants, priming immunologic memory and leading to a booster response to subsequent doses. These vaccines provide long - lasting immunity Nasopharnygeal carriage rates may also be decreased, reducing bacterial transmission. Induce herd immunity through protection from nasopharyngeal carriage. The conjugated polysaccharide vaccine is contraindicated in patients with a known hypersensitivity to any component of the vaccine, including diphtheria toxoid and in patients with a history of a severe reaction to any other vaccine containing similar components

Recommendations for use of meningococcal vaccine Routine vaccination is recommended for certain high - risk groups, including persons who have terminal complement component deficiencies and those who have anatomic or functional asplenia. Travelers above 18 months of age going to an area experiencing an epidemic or to areas with a high rate of endemic disease. Revaccination may be indicated for persons at high risk for infection particularly for children who were first vaccinated when they were less than four years of age; such children should be considered for revaccination after 2 - 3 years if they remain at high risk. Routine childhood vaccination with the meningococcal polysaccharide vaccine is not recommended because of its relative ineffectiveness in young children below two years of age. Large scale coverage with current vaccines does not provide sufficient “herd immunity”. Consequently, WHO does not currently recommend meningococcal polysaccharide vaccine as part or routine infant immunization. Routine vaccination with the vaccine is recommended for certain high - risk groups, including persons who have terminal complement component deficiencies and those who have anatomic or functional asplenia. Laboratory personnel and healthcare workers who are exposed routinely to Neisseria meningitidis in solutions that may be aerosolized should also be considered for vaccination. Vaccination with a single dose of polysaccharide vaccine is recommended for travellers above 18 months of age going to an area experiencing an epidemic of meningococcal disease or to areas with a high rate of endemic meningococcal disease. Since the epidemic of meningococcal disease that occurred in 1987 during the Hajj in Mecca, proof of vaccination against meningococcus has been required for the pilgrims to the Hajj or Umra, at their entry in Saudi Arabia. More information concerning geographic areas for which vaccination is recommended can be obtained from internet (http : //www. cdc. gov/travel/). Revaccination may be indicated for persons at high risk for Laboratory personnel and healthcare workers who are exposed routinely to Neisseria meningitidis in solutions that may be aerosolized should also be considered for vaccination.

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