1 Neisseria Nicole Luke-Marshall, Ph.D. [email protected] March 5, 2014 MIC 301 INTRODUCTION Neisseria spps. are a family of bacteria that primarily reside as normal flora on mucosal surfaces The most significant human pathogens of this genus are: an agent of septicemia and meningitis and the causative agent of gonorrhea Key Points to Remember may be transient whereas is always infections: whereas infections: . GENERAL CHARACTERISTICS § Gram-negative diplococci § Fastidious growth requirements • Grow optimally at 370C in 5% CO2 • Require highly enriched media § Fragile • do not survive well in hostile growth conditions: § Cold/hot temperatures § UV light § Dry/arid conditions Neisseria meningitidis: The Meningococcus (MC) Neisseria meningitidis Five important points to remember: 1. Humans are the only natural host 2. Colonize the upper respiratory tract 3. Transmitted via large droplet respiratory secretions § ~10% healthy adult humans are colonized § Despite exposure/colonization, few develop disease 4. A life-threatening cause of meningitis & sepsis 5. Produce a CAPSULE2 The Meningococcal Capsule 1. A large, structured, polysaccharide layer surrounding the outside of the bacterial cell. 2. Protects against host immune factors and desiccation 3. Important for invasive disease 4. Used to group N. meningitidis into 13 serogroups 5. Serogroups A, B, C, X, Y, & W135 are the most pathogenic 6. May be immunogenic and elicit protective antibodies. What is Meningococcal Disease? 1. Caused by infection with N. meningitidis. 2. Results in a high mortality rate, even with treatment. 3. Cause of life-threatening meningitis and sepsis (blood infection) • MENINGITIS: Bacterial infection of the meninges, the membranes that surround the brain and spinal cord • MENINGOCOCCEMIA: Bacterial infection of the blood/other body organs, a form of septicemia 4. Meningitis and meningococcemia are major causes of illness, death, and disability worldwide. Transmission § Spread from person-to-person via direct contact with respiratory secretions o Saliva, sputum or nasal mucus § Requires close contact with an infected person/carrier, including: o Kissing o Sharing items that touch the mouth (drinks/eating utensils/cigarettes/chapstick) o Being within 3 – 6 ft of an infected person who is coughing & sneezing Risk Factors Additional risk factors for the development of MC colonization & disease: § Crowded living areas (college dormitories, military barracks) § Not getting enough sleep (weakened immune system) § Exposure to cigarette smoke (active or passive) § Arid living conditions § Alcohol use § Viral upper respiratory tract infection § Travel to endemic areas (esp. sub-Saharan Africa and Mecca) § Compromised immune system Epidemiology-1 1. 6 of 13 capsule serogroups cause human disease: A, B, C, X, Y, W135 2. MC cause sporadic disease, community outbreaks, large epidemics § 250K to 500K cases per year worldwide (increases if epidemic) § Epidemics occur every 8-14 years in the African "meningitis belt § 800 – 1200 cases per year in the U.S. (since 2005) 3. High case-fatality rate (even with antimicrobial therapy) § Children between the ages of 6 months - 4 years are highly susceptible 4. Meningococcal disease usually presents clinically as one of three syndromes: meningitis (50.2%), bacteremia (37.5%), or bacteremic pneumonia (9.2%) 5. Leading cause of bacterial meningitis in young adults 19-27 years old. Epidemiology-2 Epidemic outbreaks (i.e., African “meningitis belt”) : - primarily caused by serotype A, followed by W-135, C, X Sporadic outbreaks: - caused by serotypes B and C, followed by W-135, Y, A Disease rates peak winter through early spring (Dec – June)3 Epidemiology-3 10% - 50% of infected people die despite receiving antibiotic treatment Survivors often have permanent problems • Loss of limbs • Deafness and/or blindness • Mental retardation • Strokes/seizures • Behavioral issues/personality changes CLINICAL MENINGOCOCCAL DISEASE -1 Following aspiration of N. meningitidis: 1. The bacteria may be eliminated or colonize the nasopharynx. 2. Colonized individuals may remain asymptomatic “carriers” or develop a mild/moderate sore throat. Pneumonia may develop. CLINICAL MENINGOCOCCAL DISEASE -2 3. In some cases (less than 1%), the bacteria cross the mucosal barrier and enter the bloodstream or the CSF resulting in either: Mild disease – a self-limited bacteremic illness characterized by fever and malaise, symptoms resolve in 1 – 2 days Serious disease – infection may progress to meningococcemia and/or meningococcal meningitis or Acute Meningococcemia Meningococcemia (Meningococcal septicemia) 1. Virulent N. meningitidis invade into the bloodstream 2. Symptoms are initially similar to influenza infection and include: • fever, nausea, headache, muscle/joint pain, chills, diarrhea, malaise 3. MC in the bloodstream results in an aggressive systemic response: • small blood vessel damage results in small hemorrhages (petechiae) • in severe infections, further damage to blood vessels can cause vascular collapse and larger hemorrhages (purpura fulminans) Petichiae and Purpura Fulminant Meningococcemia 1. Severe systemic infection characterized by rapid circulatory collapse and progressive multi-organ failure 2. Occurs in 5% - 15% of patients with acute meningococcemia 3. Abrupt onset of symptoms, including sudden appearance of widespread hemorrhagic skin lesions (hemorrhagic rash) 4. No signs of meningitis are typically present 5. Very high concentrations of MC in the bloodstream 6. High mortality (~50%) within 12 - 24 h of onset, despite antibiotic therapy4 Meningococcal Meningitis Symptoms may include: Ø Sudden onset of severe headache, high fever, malaise, chills, vomiting Ø Progressive stiffness of the neck, back and shoulders Ø Neurologic issues § light sensitivity (photophobia) § altered mental status Ø Convulsions/coma Ø Petechiae or purpura may or may not be present Ø 10% - 25% of cases are fatal even with treatment Ø