The document summarizes meningitis, including its classification, etiology, and most common bacterial pathogens based on age and risk factors. It discusses acute bacterial meningitis caused by various bacteria like Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Streptococcus agalactiae, and aerobic gram-negative bacilli. It also discusses aseptic meningitis and various infectious agents that can cause it like viruses, bacteria, fungi and parasites.

1. Meningitis Sorokhan MD, PhD Bukovinian State Medical University Department of the infectious diseases and epidemiology

2. Meningitis Meningitis is a clinical syndrome characterized by inflammation of the brain membrane and characterized by headache, nuchal rigidity, photophobia and CSF changes. Depending on the duration of symptoms, meningitis may be classified as acute or chronic. Acute meningitis denotes the evolution of symptoms within hours to several days, while chronic meningitis has an onset and duration of weeks to months. The duration of symptoms of chronic meningitis is characteristically at least 4 weeks.

3. Etiology Meningitis can also be classified according to its etiology. Acute bacterial meningitis denotes a bacterial cause of this syndrome. This is usually characterized by an acute onset of meningeal symptoms and neutrophilic pleocytosis. Depending on the specific bacterial cause, the syndrome may be called, for example, Streptococcus pneumoniae meningitis, meningococcal meningitis, or Haemophilus influenzae meningitis. Fungal and parasitic causes of meningitis are also termed according to their specific etiologic agent, such as cryptococcal meningitis, Histoplasma meningitis, and amebic meningoencephalitis.

4. Etiology Aseptic meningitis is a broad term that denotes a non-pyogenic cellular response, which may be caused by many different etiologic agents. In many cases, a cause is virus (eg, enterovirus meningitis, herpes simplex virus [HSV] meningitis). It can also be caused by bacterial, fungal, mycobacterial, and parasitic agents.

5. The Most Common Bacterial Pathogens Based on Age and Predisposing Risks S. pneumoniae, N. meningitidis, H. Influenzae Age 18-50 years S . Pneumoniae , N . Meningitidis , L . Monocytogenes , Aerobic gram-negative bacilli . Age older than 50 years N. meningitidis, S. pneumoniae, H. influenzae. Age 3 months to 18 years S. agalactiae, E. coli, H. influenzae, S. pneumoniae, N. meningitidis Age 4-12 weeks S. agalactiae (group B streptococci), E. coli , L. monocytogenes Age 0-4 weeks Bacterial Pathogen Risk and/or Predisposing Factor

6. The Most Common Bacterial Pathogens Based on Age and Predisposing Risks Coagulase-negative staphylococci, S. aureus, Aerobic gram-negative bacilli, Propionibacterium acnes. CSF shunts S. pneumoniae, H. influenzae Group A streptococci. Basilar skull fracture Staphylococcus aureus, Coagulase-negative staphylococci, Aerobic gram-negative bacilli, including Pseudomonas aeruginosa. Intracranial manipulation, including neurosurgery S. pneumoniae, N. meningitidis L. monocytogenes , Aerobic gram-negative bacilli. Immunocompromised state Bacterial Pathogen Risk and/or Predisposing Factor

8. Acute bacterial meningitis caused by S. pneumoniae S. pneumoniae, a gram-positive coccus, remains an important bacterial pathogen in humans. It is a common colonizer of the human. It causes meningitis by escaping the local host defenses and phagocytic mechanisms, either through choroid plexus seeding from bacteremia or through direct extension from sinusitis or otitis media. Presently, it is the most common bacterial cause of meningitis. It may be associated with other foci of infection, such as pneumonia, sinusitis, or endocarditis. Patients with hyposplenism, hypogammaglobulinemia, multiple myeloma, glucocorticoid treatment, defective complement (C1-C4), diabetes mellitus, renal insufficiency, alcoholism, malnutrition, and chronic liver disease are at increased risk. Pneumococcal meningitis in a patient with alcoholism. Courtesy of the CDC/Dr. Edwin P. Ewing, Jr.

9. Pneumococci organism

10. N. meningitis is a gram-negative diplococcus that is carried in the nasopharynx of otherwise healthy individuals. It initiates invasion by penetrating the airway epithelial surface. Presently, it is the leading cause of bacterial meningitis and meningococcemia in children and young adults. Risk factors include (1) deficiencies in terminal complement components (C5-C9); (2) properdin defects that increase the risk of invasive disease; (3) household crowding, chronic medical illness, corticosteroid use, and active or passive smoking; and (4) overcrowding, as is observed in college dormitories and military facilities, which has been reported for a clustering of cases. Acute bacterial meningitis caused by N. meningitis

11. A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions.

12. The leg of a 9-month-old infant in septic shock with a rapidly evolving purpuric rash.

13. Neisseria meningitis purpuric lesions on the ear and cheek of a 9-month-old infant who is in septic shock.

14. Lesions caused by Neisseria meningitis bacteremia on the palm of the hand of a 9-month-old infant.

15. Scattered petechial lesions in a patient with acute meningococcemia.

16. The legs of a 22-year-old woman in septic shock with a rapidly evolving purpuric rash.

17. Purpuric lesions in a young adult with fulminant meningococcemia.

18. Purpuric lesions in a young adult with fulminant meningococcemia.

19. H. influenzae is a small, pleomorphic, gram-negative coccobacilli that is frequently found as part of the normal flora in the upper respiratory tract of humans. It can spread from one individual to another by airborne droplets or direct contact with secretions. Meningitis is the most serious acute manifestation of systemic infection. This is primarily caused by the encapsulated type B strain. It primarily affects infants younger than 2 years. Its isolation in adults suggests the presence of an underlying medical disorder, including paranasal sinusitis, otitis media, alcoholism, CSF leak following head trauma, functional or anatomic asplenia, and hypogammaglobulinemia. Acute bacterial meningitis caused by H. influenzae Haemophilus influenza organism

20. L. monocytogenes is a small gram-positive bacillus that is cause of bacterial meningitis and is associated with one of the highest mortality rates. It is widespread in nature and has been isolated in the human stool of some healthy adults. Most human cases appear food-borne. It is a common food contaminant. Outbreaks have been associated with consumption of contaminated milk, and cheese. Persons at risk include pregnant women, infants and children, elderly individuals (>60 y), patients with alcoholism, adults who are immunosuppressed, individuals with chronic liver and renal disease, individuals with diabetes, and those with conditions of iron overload (eg, hemochromatosis or transfusion-induced iron overload). Acute bacterial meningitis caused by L. monocytogenes

21. S. agalactiae (group B streptococci) is a gram-positive coccus that is isolated from the lower gastrointestinal tract. It also colonizes the female genital, which explains why it is the most common agent of neonatal meningitis. It has also been reported in adults, primarily affecting individuals older than 60 years. Predisposing risks in adults include diabetes mellitus, pregnancy, alcoholism, hepatic failure, renal failure, and corticosteroid treatment. Acute bacterial meningitis caused by S. agalactiae

22. Aerobic gram-negative bacilli (eg, E. coli, Klebsiella pneumoniae, Serratia marcescens, P. aeruginosa, Salmonella species) can cause meningitis in certain groups of patients. E. coli is a common agent of meningitis among neonates. Other predisposing risk factors include (1) neurosurgical procedures or intracranial manipulation; (2) old age; (3) immunosuppression; (4) high-grade gram-negative bacillary bacteremia; and (5) disseminated strongyloidiasis, which has been reported as a classic cause of gram-negative bacillary bacteremia. Acute bacterial meningitis caused by Aerobic gram-negative bacilli

23. Staphylococcus species ( S. aureus and coagulase-negative staphylococci) are gram-positive cocci that are part of the normal skin flora. Meningitis caused by staphylococci is associated with the following risk factors: (1) status postneurosurgery and posttrauma, (2) presence of CSF shunts, and (3) infective endocarditis and paraspinal infection. Staphylococcus epidermidis is the most common cause of meningitis in patients with CNS (ie, ventriculoperitoneal) shunts. Acute bacterial meningitis caused by Staphylococcus species

24. Aseptic meningitis is the most common infectious syndrome affecting the CNS. Most episodes are caused by a viral pathogen, but they can also be caused by bacteria, fungi, or parasites. Importantly, partially treated bacterial meningitis accounts for a large number of meningitis cases with a negative microbiologic workup. Aseptic meningitis syndrome

25. Infectious Agents Causing Aseptic Meningitis Syndrome Partially-treated bacterial meningitis: L. monocytogenes Brucella species Rickettsia rickettsii Ehrlichia species Mycoplasma pneumoniae B. burgdorferi Treponema pallidum Leptospira species Mycobacterium tuberculosis Nocardia species Bacteria Agent Category

26. Infectious Agents Causing Aseptic Meningitis Syndrome Acanthamoeba species Angiostrongylus cantonensis Taenia solium (cysticercosis) Parasites Cryptococcus neoformans Candida species Aspergillus species Fungi Agent Category

27. Infectious Agents Causing Aseptic Meningitis Syndrome Enterovirus, Herpesvirus, Paramyxovirus, Togavirus, Flavivirus, Bunyavirus, Alphavirus, Reovirus, Arenavirus Rhabdovirus , Retrovirus Viruses Agent Category

28. Enterovirus belongs to the family Picornaviridae. It is classified further to include polioviruses (3 serotypes), coxsackievirus A (23 serotypes), coxsackievirus B (6 serotypes), echovirus (31 serotypes), and the newly recognized enterovirus serotypes 68-71. They are distributed worldwide, and the infection rates vary depending on the season of the year and the age and socioeconomic status of the population. The virus is usually spread by fecal-oral or respiratory routes and occurs during summer and fall in temperate climates and year-round in tropical regions. Most of the infections occur in individuals who are younger than 15 years, with the highest attack rates in children who are younger than 1 year. Acute viral meningitis

29. The Herpesviridae family consists of large DNA-containing enveloped viruses. Eight members are known to cause human infections, and all have been implicated in meningitis syndromes. HSV-1 is a cause of encephalitis, while HSV-2 more commonly causes meningitis. EBV, or HHV-4, and CMV, or HHV-5, may manifest as meningitis during the mononucleosis syndrome. Varicella zoster virus (VZV), or HHV-3, and CMV are causes of meningitis in immunocompromised hosts, especially patients with AIDS. Acute viral meningitis

30. Aseptic meningitis syndrome may be the presenting symptom in a patient with acute HIV infection. This usually is part of the mononucleosislike acute seroconversion phenomenon. Always suspect HIV as a cause of aseptic meningitis in a patient with risk factors such as intravenous drug use and in individuals who practice high-risk sexual behaviors. Acute viral meningitis

31. Patients with meningitis caused by the mumps virus usually present with the triad of fever, vomiting, and headache. It follows the onset of parotitis, which clinically resolves in 7-10 days. Adenovirus (serotypes 1, 6, 7, and 12) has been associated with cases of meningoencephalitis. Chronic meningoencephalitis has been reported with serotypes 7, 12, and 32. The infection is usually acquired through a respiratory route. Acute viral meningitis

32. Chronic meningitis M. tuberculosis, B. burgdorferi, T. pallidum, Brucella species, Francisella tularensis, Nocardia species, Actinomyces species. Bacteria C. neoformans, C. immitis, H. capsulatum, Candida albicans, Aspergillus species, Sporothrix schenckii. Fungi Acanthamoeba species, Angiostrongylus cantonensis, Schistosoma species, Echinococcus granulosus Parasites Agent Category

33. Brucella species are small gram-negative coccobacilli that cause zoonoses as a result of infection with Brucella abortus, Brucella melitensis, Brucella suis, and Brucella canis. Transmission to humans occurs following direct or indirect exposure to infected animals (eg, sheep, goat, cattle). Persons at risk include individuals who had contact with infected animals (eg, sheep, goat, cattle) or their products (eg, intake of unpasteurized milk products). Veterinarians, workers, and laboratory workers dealing with these animals are also at risk. Chronic bacterial meningitis caused by Brucella species

34. M. tuberculosis is an acid-fast bacillus that causes a broad range of clinical illnesses that can affect virtually any organ of the body. It is worldwide in distribution, and humans are its only reservoir. The presentation may be acute, but the classic presentation is subacute and spans weeks. Patients generally have a prodrome of fever of varying degrees, malaise, and intermittent headaches. Patients often develop central nerve palsies (III, IV, V, VI, and VII), suggesting basilar meningeal involvement. Chronic bacterial meningitis caused by M. tuberculosis

35. T. pallidum is a slender tightly coiled spirochete that is usually acquired by sexual contact. Other modes of transmission include direct contact with an active lesion, passage through the placenta, and blood transfusion. The median incubation period before the appearance of symptoms is 21 days (range 3-90 d), during which time spirochetemia develops. Three stages of disease are described, and involvement of the CNS can occur during any of these stages. Syphilitic meningitis usually occurs during the primary or secondary stage. Its presentation is similar to other agents of aseptic meningitis, with headache, nausea, vomiting, and meningismus Chronic bacterial meningitis caused by T. pallidum

36. B. burgdorferi is the agent of Lyme disease. Lyme disease is characterized by 3 stages. Although rare during stage I, CNS involvement (with meningitis) may occur and is characterized by the concurrent appearance of erythema migrans at the site of tick bite. More commonly, aseptic meningitis syndrome occurs 2-10 weeks following the erythema migrans rash. This represents stage 2 of Lyme disease, or the borrelial hematogenous dissemination stage. Chronic neuroborreliosis is a hallmark of the third stage of Lyme disease and is characterized by subacute encephalopathy manifested by disturbance in mood, memory, language, or sleep. Chronic bacterial meningitis caused by B. burgdorferi

37. C. neoformans is an encapsulated yeastlike fungus that is ubiquitous and has a worldwide distribution. It has been found in high concentrations in aged pigeon droppings and pigeon nesting places. The infection is characterized by the gradual onset of symptoms, the most common of which is headache. Most cases have occurred among individuals with AIDS and among organ transplant recipients. Fungal meningitis caused by C. neoformans

38. C. immitis is a dimorphic fungus that exists in mycelial and yeast (spherule) forms. The infection follows inhalation of the Arthroconidia. Extrapulmonary dissemination to the skin (most common), joints, and bones occurs in predisposed individuals. Coccidioidal meningitis is the most serious form of dissemination, and it usually is fatal if left untreated. These patients may present with headache, vomiting, and altered mental function associated with pleocytosis, elevated protein levels, and decreased glucose levels. Eosinophils may be a prominent finding in the CSF. Fungal meningitis caused by C. immitis

39. H. capsulatum is one of the dimorphic fungi that exist in mycelial and yeast forms. It is usually found in soil. Primary infection follows inhalation exposure. Dissemination occurs in individuals with underlying immune deficiency (eg, from HIV or pharmaceutical agents) and extremes of age. Patients may present with headache, cranial nerve deficits, or changes in mental status months prior to diagnosis. Fungal meningitis caused by H. capsulatum

40. Candidal species are ubiquitous in nature. They are normal commensals in humans and are found in the skin, the gastrointestinal tract, and the female genital tract. The most common species is C. albicans . Involvement of the CNS usually follows hematogenous dissemination. The most important predisposing risk for acquiring disseminated candidal infection appears to use of broad-spectrum antibiotics and indwelling devices such as urinary and vascular catheters. AIDS is also considered a predisposing risk factor. Fungal meningitis caused by Candidal species

41. The classic presentation of meningitis includes fever, headache, neck stiffness, photophobia, nausea, vomiting, and signs of cerebral dysfunction (eg, lethargy, confusion, coma). These symptoms may develop later in the course of illness in some patients who may initially present with atypical symptoms such as leg pain and cold hands and feet. The triad of fever, nuchal rigidity, and change in mental status is found in only two thirds of patients. Signs and symptoms

42. The classic presentation of acute meningitis is the onset of symptoms within hours to a few days, compared to weeks for chronic meningitis. Atypical presentation may be observed in certain groups. Elderly individuals, especially those with underlying comorbidities (eg, diabetes, renal and liver disease), may present with lethargy and an absence of meningeal symptoms. Patients with neutropenia may present with subtle symptoms of meningeal irritation. Other immunocompromised hosts, including organ and tissue transplant recipients and patients with HIV and AIDS, may also have an atypical presentation. Signs and symptoms

43. Signs and symptoms

44. The diseases most frequently confused with meningitis are brain abscess, meningeal carcinomatosis, CNS vasculitis, stroke, encephalitis. Differential Diagnoses

45. CSF findings in different forms of meningitis usually mononucle high low Malignant < 300/mm³ high low Fungal mononuclear and PMNs, < 300/mm³ high low Tuberculous mononuclear , < 300/mm³ normal or high normal Acute viral PMNs , often > 300/mm³ high low Acute bacterial Cells Protein Glucose Type of meningitis

47. Treatment: b acterial meningitis Empiric antibiotics must be started immediately, even before the results of the lumbar puncture and CSF analysis are known. The choice of initial treatment depends largely on the kind of bacteria that cause meningitis in a particular place.

48. Treatment: viral meningitis Viral meningitis typically requires supportive therapy only; most viruses responsible for causing meningitis are not amenable to specific treatment. Viral meningitis tends to run a more benign course than bacterial meningitis.

49. Treatment: fungal meningitis Fungal meningitis, such as cryptococcal meningitis, is treated with long courses of highly dosed antifungals , such as amphotericin B and flucytosine . Raised intracranial pressure is common in fungal meningitis, and frequent (ideally daily) lumbar punctures to relieve the pressure are recommended, or alternatively a lumbar drain.

50. Prognosis Patients with viral meningitis usually have a good prognosis for recovery. The prognosis is worse for patients at the extremes of age (ie, <2 y, >60 y) and those with significant comorbidities and underlying immunodeficiency. Patients presenting with an impaired level of consciousness are at increased risk for developing neurologic sequelae or dying. A seizure during an episode of meningitis also is a risk factor for mortality or neurologic sequelae.

51. Thank you for your attention!