Case Study Pathogenic Bacteriology 2009 Case # 42 Mamadou Diallo Anne Roberts Case Summary 19 year old male student with normal health went to bed with a fever/headache Fever of 40˚c Neck was supple Purpuric rash on legs, trunk and wrists CSF glucose, protein and white blood cell were normal. Blood culture grew the organism. Key Information Pointing to Diagnosis PHYSICAL EXAMINATION 19 years old, student Purpuric rash on legs, wrist, trunk Supple neck LABORATORY EXAMINATION CSF glucose, protein, and white blood cell was normal (indicates no bacteria in the CSF fluid) Organism was cultured from blood – Gram Negative Diplococci Low platelet count – indicates the intravascular coagulation The Diagnosis for Case #42 The patient was diagnosed with bacterial meningitis. The causative agent of this infection was Neisseria meningitidis. The purpuric rash, and Gram stain results were key in the diagnosis of the patient. The finding of a normal CSF profile without evidence of meningitis is atypical. Usually a culture of this fluid will indicate the presence of bacteria. This meant that the organism had disseminated to the blood, where it was cultured. Classification,Gram Stain Results, and Microscopic Appearance of N. meningitidis Family – Neisseriaceae Genus – Neisseria Species – meningitidis Gram Negative Diplococci Can be NF of oropharynx in 40% of adults. These carriers demonstrate no symptoms of meningitis and are primary source of spread through aerosols, exchange of saliva, etc . Diseases and Pathogenesis Caused by Neisseria meningitidis Pathogenesis: N. meningitidis will attach to epithelial cells of nasopharynx and invade mucous membranes. Bacteria enter blood stream, travel through body where Type IV pili will allow organism to attach to meninges in brain Invasion of the blood stream occurs with individuals deficient in complement component (C5- C8) Lipooligosaccharide (LOS) damages host tissue - hemorrhaging of blood into skin and mucous membranes (purpuric rash) Activity of LOS elicits host inflammatory response Diseases: Endemic and epidemic cerebral meningitis Waterhouse Friderichen syndrome – hemorrhaging into adrenal glands Meningiococcal pneumonia Capsular antigens A, B, C, Y, W135 are cause of illness. Diagnosis/Isolation/Identification of Neisseria meningitidis Diagnosis: Neck pain, purpuric rash Gram stain of the blood culture Gram stain from skin lesions Isolation: Growth on chocolate agar with 5 - 10% CO2 MTM agar Identification: Oxidase – Negative Catalase - Positive Nitrate Reduction – Positive Growth on MTM Carbohydrate utilization tests - Glucose and Maltose positive Therapy, Prevention and Prognosis of Patient Infected with N. meningitidis Prophylactic strategies in large populations: Administer the tetravalent vaccine to capsular antigens A, C, Y, W135 ( group B vaccine not available in U.S) This is recommended to individuals living in colleges and military settings Prophylactic Strategies to exposed individuals: Isolate infected individuals Antimicrobial therapy imperative – fatal if individual goes untreated Penicillin, Chloramphenicol, erythromycin Prophylaxis with rifampin, ciprofloxacin or ceftriaxone for household and others with close contacts. Primary Research Article : Neisseria meningitidis Zarantonelli, Maria, et al. 2006. Differential Role of LOS of N. meningitidis in Virulence & Inflammatory Response During Respiratory Infection in Mice, Infection and Immunity, OCT: 5506-5512. Experimental: Two mutant strains: double knock out and a single of the gene expressing the LOS from ( N. meningitidis serogroupB) – Mutant and wild type strain injected in a mouse model to observe the effect of LOS alteration in meningococcal virulence and its role in inducing an inflammatory response. What did they find? – – – Mutant devoid of LOS unable to invade / persist in the bloodstream Lack of LOS makes N. meningitidis more susceptible to complement mediated bacteriolysis and opsonophagocytosis – mechanisms of early innate defense. The mutant devoid of LOS was also unable to induce an inflammatory response Primary Research Article : Neisseria meningitidis In conclusion Take Home Message This type of meningitis involves N. meningitidis Typical symptoms: Purpuric rash, supple neck, fever Pathogen can: Disseminate into the blood stream, causing serious complications Diagnostics: Gram stain of CSF/blood culture/skin lesions Therapy is based: Penicillin, Chloramphenicol Prognosis is: Fatal without antimicrobial therapy Prevention: Get Tetravalent vaccine!!!! Transmission: Aerosols, exchange of saliva, etc. Threat: Endemic and epidemic threat among large populations, mental retardation, loss of limbs References Mahon, Connie, Donald Lehman, George Manuselis. Textbook of Diagnostic Microbiology. 3rd Edition. Saunders-Elsevier, St. Louis, Missouri, 2007. Zarantonelli, Maria, et al. 2006. Differential Role of LOS of N. meningitidis in Virulence & Inflammatory Response During Respiratory Infection in Mice, Infection and Immunity, OCT: 5506-5512.