Neisseriaceae: Gram-Negative Cocci

Neisseriaceae: Gram-Negative Cocci of Clinical Importance

• The family Neisseriaceae consists of 5 genera: Neisseria, Kingella, Eikenella, Simonsiella, and Alysiella.
• Neisseria genus includes pathogens like Neisseria meningitidis and Neisseria gonorrhoeae, and commensal like Neisseria lactamica.

General Characteristics of Neisseriaceae

• Gram-negative cocci, often diplococci with adjacent sides flattened.
• Associated with mucous membranes of warm-blooded animals.
• Twitching motility via Type IV pili.
• Oxidase positive and capnophilic, requiring 5-10% CO2 for growth.
• Acid from oxidation of carbohydrates, not from fermentation.

Neisseria Meningitidis

• Pathogen that causes meningitis and septicaemia.
• Asymptomatic commensal of the human upper respiratory tract (URT).
• High morbidity and mortality, with sporadic or epidemic outbreaks.
• The human nasopharynx is the sole ecological niche.
• Spreads via saliva – direct contact/droplet spread.
• Proliferation/horizontal gene exchange, and genetic reassortment during carriage result in many phenotypes.

Neisseria Gonorrhoeae

• Pathogen that causes gonorrhoea, primarily infecting the urogenital epithelia.
• Usually sexually transmitted, with rare cases of disseminated infection.
• Non-capsulated, with a type IV pili major virulence factor.
• Outer membrane: lipooligosaccharide (LOS) and surface protein OPA.
• Discharge from the genitals, burning when peeing, and asymptomatic in women.
• Transmitted from mother to baby during birth, causing conjunctivitis.

Epidemiology of Gonorrhoea

• Mainly affects people in their 20s, with an increasing incidence in the UK.
• Over 78 million cases worldwide each year, with a lack of understanding of the complex transmission routes and reservoirs.

Antibiotic Resistance in Gonorrhoea

• Increased azithromycin resistance in the UK, leading to the possibility of untreatable gonorrhoea.
• Dual antimicrobial therapy (Azithromycin and ceftriaxone) required.
• Increased surveillance of strains and resistance necessary.

Laboratory Diagnosis

• Meningococcal disease: CSF and blood samples, microscopy, culture, PCR, and detection of soluble bacterial polysaccharides in CSF by latex agglutination.
• Gonococcal disease: endocervical, cervical, anal, and eye swabs, and urines, with nucleic amplification tests (strand displacement amplification assay) and QRT PCR.

Prevention and Control

• Introduction of MenAfriVac (serogroup A meningococcal conjugate vaccine) for Africa has been a massive public health success.
• Must introduce MenAfriVacR into the national childhood immunization program.
• How long this protection will persist needs to be established.

Meningococcal Disease and Prevention

• Carriage of N. meningitidis in the nasopharynx is crucial in understanding the disease and prevention, with 10-35% of university students carrying the bacteria.
• Pathogenesis of N. meningitidis involves invasive phenotypes expressing factors needed to invade the bloodstream, including lipooligosaccharide (LOS), type IV pili, surface proteins NadA and Opa, invasins, and iron-acquisition.
• Meningococcal meningitis symptoms include vomiting, intense headache, confusion, drowsiness, fever, sensitivity to light, skin rash, and eventually, convulsions and stiff neck.
• Meningitis is inflammation of the meninges, which can lead to fluid buildup in the brain ventricles, causing loss of consciousness or death if left untreated.
• Vaccines are available to combat meningococcal disease, including quadrivalent A, C, Y, W-135 polysaccharide vaccines, which are effective in outbreak control.
• Multicomponent vaccines exist but fall short of combating all virulent strains.

N. meningitidis vs. N. gonorrhoeae

• N. meningitidis is an asymptomatic commensal of the human upper respiratory tract, causing meningitis and septicaemia.
• N. gonorrhoeae is usually transmitted sexually, infecting the urogenital epithelia, and can cause epididymitis, cervicitis, endometritis, and PID.
• Both organisms have genetic and antigenic similarities but very different lifestyles.

Carriage and Invasion of N. meningitidis

• The human nasopharynx is the sole ecological niche for N. meningitidis.
• Carriage of N. meningitidis allows for horizontal gene exchange and genetic reassortment, resulting in many phenotypes.
• For genetically primed strains, invasion can occur, but most carriage is not associated with disease.

Prevention and Control

• Introduction of MenAfriVac (serogroup A meningococcal conjugate vaccine) has been a massive public health success in Africa, with virtual elimination of serogroup A meningitis and epidemics.
• Vaccination has prevented serogroup A invasive meningococcal disease and carriage in Chad.
• Surveillance of strains and resistance are required to monitor the effectiveness of vaccines.

Gonorrhoea

• Gonorrhoea mainly affects people in their 20s, with increasing incidence in the UK.
• Transmission occurs via unprotected vaginal, oral, or anal sex.
• Symptoms include discharge from the genitals, burning when peeing, and women are often asymptomatic.
• Gonorrhoea can be transmitted from mother to baby during birth, causing conjunctivitis.

Antibiotic Resistance in Gonorrhoea

• Increased azithromycin resistance in the UK has led to the possibility of untreatable gonorrhoea.
• Dual antimicrobial therapy (azithromycin and ceftriaxone) is recommended.
• Sub-therapeutic dosing in Asia and the UK has contributed to antibiotic resistance.

Laboratory Diagnosis

• Meningococcal disease diagnosis involves CSF and blood samples, microscopy, culture, PCR, and detection of soluble bacterial polysaccharides in CSF.
• Gonococcal disease diagnosis involves endocervical, cervical, anal, and eye swabs, and urines, as well as nucleic amplification tests and culture.

Treatment

• Meningococcal disease treatment involves IV antibiotics (benzyl penicillin or amoxicillin), and maintenance therapy for shock (fluids, etc.).
• Gonococcal disease treatment involves dual therapy with ceftriaxone and azithromycin due to antibiotic resistance.