Neisseria Microbiology Department 2024-2025 PDF

Ninevah University Medicine College Microbiology Department 2024 - 2025 Dr. Saba Abdul Salam Hamid Al-Sultan [email protected]  4. Neisseria (Gram Negative Cocci) The lecture overview about Pathogenesis , Epidemiology ,...

Ninevah University Medicine College Microbiology Department 2024 - 2025 Dr. Saba Abdul Salam Hamid Al-Sultan [email protected]  4. Neisseria (Gram Negative Cocci) The lecture overview about Pathogenesis , Epidemiology , Clinical findings and laboratory diagnosis of Neisseria meningitidis & Neisseria gonorrhoeae P:2  1. Neisseria meningitidis Pathogenesis & Epidemiology Humans are the only natural hosts for meningococci. The organisms are transmitted by airborne droplets; they colonize the membranes of the nasopharynx and become part of the transient flora of the upper respiratory tract. Carriers are usually asymptomatic. From the nasopharynx, the organism can enter the bloodstream and spread to specific sites, such as the meninges or joints, or be disseminated throughout the body (meningococcemia). P:3  1. Neisseria meningitidis Pathogenesis & Epidemiology About 5% of people become chronic carriers and serve as a source of infection for others. The carriage rate can be as high as 35% in people who live in close quarters (e.g., military recruits); this explains the high frequency of meningitis outbreaks in the armed forces before the use of the vaccine. The carriage rate is also high in patients’ close (family) contacts. Outbreaks of meningococcal disease also have occurred in college students living in dormitories. P:4  Two organisms cause more than 80% of cases of bacterial meningitis in infants older than 2 months of age: Streptococcus pneumoniae and N meningitidis. Of these organisms, meningococci, especially those in group A, are most likely to cause epidemics of meningitis. Group B meningococci cause many cases of meningitis in developed countries. Overall, N meningitidis ranks second to S. pneumoniae as a cause of meningitis but is the most common cause in persons between the ages of 2 and 18 years. P:5 Meningococci have three important virulence factors: ( 1) A polysaccharide capsule that enables the organism to resist phagocytosis by polymorphonuclear leukocytes (PMNs). (2) Endotoxin, which causes fever, shock, and other pathophysiologic changes(in purified form, endotoxin can reproduce many of the clinical manifestations of meningococcemia). (3) An immunoglobulin A (IgA) protease that helps the bacteria attach to the membranes of the upper respiratory tract by cleaving secretory IgA. P:6 Clinical Findings The two most important manifestations of disease are meningococcemia and meningitis. The most severe form of meningococcemia is the life threatening Waterhouse-Friderichsen syndrome, which is characterized by high fever, shock, widespread purpura, disseminated intravascular coagulation, thrombocytopenia, and adrenal insufficiency. Bacteremia can result in the seeding of many organs, especially the meninges. The symptoms of meningococcal meningitis are those of typical bacterial meningitis, namely, fever, headache, stiff neck, and an increased level of PMNs in spinal fluid. P:7  Laboratory Diagnosis The principal laboratory procedures are smear and culture of blood and spinal fluid samples. A presumptive diagnosis of meningococcal meningitis can be made if gram-negative cocci are seen in a smear of spinal fluid. The organism grows best on chocolate agar incubated at 37°C in a 5% CO2 atmosphere. A presumptive diagnosis of Neisseria can be made if oxidase- positive colonies of gram-negative diplococci are found. The differentiation between N. meningitidis and N gonorrhoeae is made on the basis of sugar fermentation: P:8  Laboratory Diagnosis meningococci ferment maltose, whereas gonococci do not (both organisms ferment glucose). Immunofluorescence can also be used to identify these species. Tests for serum antibodies are not useful for clinical diagnosis. However, a procedure that can assist in the rapid diagnosis of meningococcal meningitis is the latex agglutination test, which detects capsular polysaccharides in the spinal fluid. P:9 2. Neisseria gonorrhoeae Pathogenesis & Epidemiology Gonococci, like meningococci, cause disease only in humans. The organism is usually transmitted sexually; newborns can be infected during birth. Because gonococcus is quite sensitive to dehydration and cool conditions, sexual transmission favors its survival. Gonorrhea is usually symptomatic in men but often asymptomatic in women. Genital tract infections are the most common source of the organism, but anorectal and pharyngeal infections are important sources as well. P : 10 2. Neisseria gonorrhoeae Pili constitute one of the most important virulence factors, because they mediate attachment to mucosal cell surfaces and are antiphagocytic. Piliated gonococci are usually virulent, whereas nonpiliated strains are avirulent. Two virulence factors in the cell wall are endotoxin. (.Lipopolysaccharide, LOS) and the outer membrane proteins. P : 11  The organism's IgA protease can hydrolyze secretory lgA, which could otherwise block attachment to the mucosa. Gonococci have no capsules. The main host defenses against gonococci. are antibodies (IgA and IgG), complement, and neutrophils. Antibody-mediated opsonization and killing within phagocytes occur, but repeated gonococcal infections are common, primarily as a result of antigenic changes of pili and the outer membrane proteins. P : 12  Gonococci infect primarily the mucosal surfaces ( e.g., the urethra and vagina), but dissemination occurs. Certain strains of gonococci cause disseminated infections more frequently than others. The most important feature of these strains is their resistance to being killed by antibodies and complement. The mechanism.of this "serum resistance" is uncertain, but the presence of a porin protein (porin A) in the cell wall, which inactivates the C3b component of complement, appears to play an important role. P : 13  Clinical Findings Gonococci cause both localized infections, usually in the genital tract, and disseminated infections with seeding of various organs. Gonococci reach these organs via the bloodstream (gonococcal bacteremia). Gonorrhea in men is characterized primarily by urethritis accompanied by dysuria and a purulent discharge , Epididymitis can occur. In women, infection is located primarily in the endocervix, causing a purulent vaginal discharge and intermenstrual bleeding (cervicitis). P : 14  Clinical Findings The most frequent complication in women is an ascending infection of the uterine tubes (salpingitis, PID : Pelvic inflammatory disease), which can result in sterility or ectopic pregnancy as a result of scarring of the tubes. Disseminated gonococcal infections (DGI) commonly manifest as arthritis, tenosynovitis, or pustules in the skin. Disseminated infection is the most common cause of septic arthritis in sexually active adults. The clinical diagnosis of DGI is often difficult to confirm using laboratory tests because the organism is not cultured in more than 50% of cases. P : 15  Other infected sites include the anorectal area, throat, and eyes. Anorectal infections occur chiefly in women and homosexual men. They are frequently asymptomatic, but a bloody or purulent discharge (proctitis) can occur. In the throat, pharyngitis occurs, but many patients are asymptomatic. In newborn infants, purulent conjunctivitis (ophthalmia neonatorum) is the result of gonococcal infection acquired from the· mother during passage through the birth canal. P : 16  The incidence of gonococcal ophthalmia has declined greatly in recent years because of the widespread use of prophylactic erythromycin eye ointment ( or silver nitrate) applied shortly after birth. Gonococcal conjunctivitis also occurs in adults as a result of the transfer of organisms from the genitals to the eye. Other sexually transmitted infections ( e.g., syphilis and nongonococcal urethritis caused by Chlamydia trachomatis) can coexist with gonorrhea; therefore, appropriate diagnostic and therapeutic measures must be taken. P : 17 Laboratory Diagnosis The diagnosis of urogenital infections depends on Gram staining and culture of the discharge. However, nucleic acid amplification tests are widely used as screening tests. In men, the finding of gram-negative diplococci within PMNs in a urethral discharge specimen is sufficient for diagnosis. In women, the use of the Gram stain alone can be difficult to interpret; therefore, cultures should be done. Gram stains on cervical specimens can be falsely positive because of the presence of gram-negative diplococci in the normal flora and can be falsely negative because of the inability to see small numbers of gonococci when using the oil immersion lens. Cultures must also be used in diagnosing suspected pharyngitis or anorectal infections. P : 18  Specimens from mucosal sites, such as the urethra and cervix, are cultured on Thayer-Martin medium, which is a chocolate agar containing antibiotics (vancomycin, colistin, trimethoprim, and nystatin) to suppress the normal flora. The finding of an oxidase-positive colony composed of gram-negative diplococci is sufficient to identify the isolate as a member of the genus Neisseria. Specific identification of the gonococcus can be made either by its fermentation of glucose (but not maltose) or by fluorescent-antibody staining. Note that specimens from sterile sites, such as blood or joint fluid, can be cultured on chocolate agar without antibiotics because there is no competing normal flora. P : 19  Two rapid tests that detect the presence of gonococcal nucleic acids in patient specimens are widely used as a screening test. These tests are highly sensitive and specific. In one type of test, the gonococcal nucleic acids are amplified ( amplification tests), and in the other type, they are not amplified. Note that serologic tests to determine the presence of antibody to gonococci in the patient's serum are not useful for diagnosis. P : 20 Dr. Saba Al-Sultan P : 21