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Harrison’s Manual of Medicine



Meningococcal Infections
Listerial Infections

EPIDEMIOLOGY   Neisseria meningitidis causes two life-threatening diseases: meningococcal meningitis and fulminant meningococcemia. Meningococci also cause pneumonia, septic arthritis, pericarditis, urethritis, and conjunctivitis.
N. meningitidis is a gram-negative diplococcus with a polysaccharide capsule. Humans are the only host for the organism, and transmission is via droplet respiratory secretions. Meningococcal colonization of the nasopharynx is more common than invasive disease and can persist for months; in nonepidemic periods, ~10% of healthy individuals are colonized. Factors predisposing to colonization include residence in a household with a person who has meningococcal disease or is a carrier, household or institutional crowding, active or passive exposure to tobacco smoke, and a recent viral URI. These factors are also associated with an increased risk of invasive disease. The attack rate for sporadic meningococcal disease is ~1 case per 100,000 persons per year; the peak incidence coincides with the winter peak of respiratory viral illnesses. Attack rates are higher for children than for adults and are highest among infants 3–9 months of age. There is a second peak of incidence among teenagers. The secondary attack rate among households is 400 to 1000 cases per 100,000 household members. Most secondary cases occur within 2 weeks of the primary case, but some develop up to several months later.
Meningococcal disease occurs worldwide as sporadic cases, institutional or community outbreaks, and large epidemics. Meningococci are classified traditionally by the serogroup method, which reflects the antigenicity of their capsular polysaccharides. Five serogroups (A, B, C, Y, and W-135) account for >90% of cases. In the U.S., endemic disease is caused most often by serogroup B, while serogroup C is a more frequent cause of outbreaks. Serogroup Y has been isolated from almost one-third of cases in the U.S.; the pts involved are generally older and have underlying illnesses. Other meningococcal classification methods are based on molecular typing and genomic sequencing.
PATHOGENESIS   Meningococci that colonize the respiratory tract rarely traverse the mucosa to enter the bloodstream. If multiplication in the blood occurs slowly, the bacteria seed local sites (e.g., meninges, joints). More rapid multiplication is associated with DIC and shock. N. meningitidis has a striking tropism for the meninges. Host defense mechanisms include serogroup-specific bactericidal antibodies and complement.
CLINICAL MANIFESTATIONS   Meningococcemia   Between 10 and 30% of pts who develop meningococcal disease have bacteremia without meningitis. Occasionally, there is a prodromal syndrome of sore throat and upper respiratory symptoms. Manifestations of meningococcemia include fever, chills, nausea, vomiting, and myalgias. Rash is the most distinctive feature, with erythematous macules that rapidly become petechial and, in severe cases, purpuric. The lesions are typically located on the trunk and lower extremities but may also occur on the face, arms, and mucous membranes. Fulminant disease (the Waterhouse-Friderichsen syndrome) is marked by shock, DIC-induced microthrombosis, hemorrhage, and tissue injury. Chronic meningococcemia is a rare syndrome of episodic fever, maculopapular or petechial rash, and arthralgias that can last from weeks to months. If untreated or treated with glucocorticoids, it may evolve into meningitis, fulminant meningococcemia, or (rarely) endocarditis.
Meningitis   In general, pts with meningococcal meningitis have been sick for ³24 h before seeking medical attention. Symptoms are similar to those caused by other meningeal pathogens and include nausea, vomiting, headache, neck stiffness, lethargy, and confusion. Many pts have concurrent meningococcemia, and the associated skin lesions may suggest the diagnosis.
Other Manifestations   Arthritis occurs in ~10% of pts with meningococcal disease and may be due to direct bacterial invasion of the joint or immune complex deposition. Rare manifestations of meningococcal infection include conjunctivitis, pneumonia (associated with serogroup Y), pericarditis, endocarditis, and urethritis.
DIAGNOSIS   Early recognition of meningococcal disease depends on distinguishing it from the other acute systemic infections that it resembles. The detection of a petechial or purpuric rash should raise diagnostic suspicion. Diagnosis depends on recovering N. meningitidis, its antigens, or its DNA from normally sterile fluids, such as blood, CSF, or synovial fluid, or from skin lesions. A Gram’s stain of CSF reveals intra- or extracellular organisms in ~85% of pts with meningococcal meningitis. The latex agglutination test for meningococcal polysaccharides is somewhat less sensitive. PCR amplification of DNA in buffy coat or CSF may be more sensitive than other tests and is not affected by prior antibiotic therapy.

Initial therapy (before the diagnosis is known) consists of cefotaxime (2 g IV q8h) or ceftriaxone (1 g IV q12h), since these drugs cover other likely bacterial pathogens besides meningococci. Penicillin G (4 million U IV q4h) is an acceptable alternative, with high-level resistance reported only in Spain. Chloramphenicol (75–100 mg/kg PO q6h) is an alternative in the b-lactam- allergic pt. Most pts with meningococcal meningitis should be treated for at least 5 days. Adjuvant glucocorticoid therapy for meningitis in adults is controversial. Pts with fulminant meningococcemia require additional IV fluids, elective ventilation, pressors, and control of bleeding.

PREVENTION   Pts who are hospitalized with meningococcal disease should be placed in respiratory isolation for the first 24 h of antibiotic therapy. Meningococcal disease in close contacts of cases (e.g., household contacts, day care center contacts, anyone with direct exposure to the pt’s secretions) can be prevented with rifampin (600 mg PO q12h for 4 doses). A single oral dose of ciprofloxacin (500 mg) or ofloxacin (400 mg) is an acceptable alternative in nonpregnant adults but not in children or pregnant women. A single dose of 250 mg of ceftriaxone IM is recommended for pregnant contacts. Casual contacts are not at increased risk. A polysaccharide vaccine active against serogroups A, C, Y, and W-135 is used to prevent infections in military recruits, persons with functional or anatomic asplenia, persons with complement deficiencies, and travelers to areas with epidemic disease and to prevent late infections in close contacts of cases.
EPIDEMIOLOGY AND PATHOGENESIS   Listeria monocytogenes, a motile gram-positive bacillus, is responsible for food-borne invasive infections, primarily sepsis and meningitis. Cases may occur sporadically or in outbreaks associated with particular foods. Implicated foods have included Mexican-style and other soft cheeses, coleslaw, pasteurized milk, and food from delicatessens. The incubation period for disease following consumption of contaminated food can be 2–6 weeks. At highest risk are pregnant women and persons immunocompromised by disease (solid or hematologic malignancies, diabetes mellitus, renal or hepatic disease, AIDS) or drugs (chronic glucocorticoid therapy), although infection occasionally occurs in immunocompetent adults, particularly elderly persons.
CLINICAL MANIFESTATIONS   Immunocompromised hosts most often present with bacteremia without an evident focus; CNS infection is less commonly the initial symptom. Pts are usually febrile and may have myalgias, nausea, vomiting, and diarrhea. Cases of bacteremia and meningitis due to Listeria cannot be distinguished clinically from those caused by other organisms. Pregnancy-associated listeriosis develops most often in the third trimester but may occur at any time; 50–66% of pregnant women have a mild illness, with fever, myalgias, malaise, and occasional GI complaints. Transplacental spread of infection can lead to chorioamnionitis, premature labor, fetal demise, or neonatal infection. Neonatal infection may be of early (<7 days) or late onset. Early-onset infection usually occurs within the first 2 days of life, with sepsis, respiratory distress, skin lesions, or disseminated abscesses involving mutliple organs. Infants with late-onset infection are more likely to have meningitis. Recent studies of common-source outbreaks have indicated that Listeria is an occasional cause of an acute diarrhea syndrome in immunocompetent persons. Listeria may also cause encephalitis, cerebritis, intracranial abscesses, and (rarely) endocarditis and other focal infections.
DIAGNOSIS   Listeriosis is diagnosed by culture of the organism from a normally sterile body site (e.g., CSF or blood). Culture from stool or vagina is not reliable because ~5% of healthy individuals carry the organism.

Nonpregnant adults with listeriosis should be treated with ampicillin (2 g IV q4h) or penicillin G (15–20 million units/d IV in 6 divided doses); immunosuppressed pts with meningitis can also receive gentamicin for synergy (1.3 mg/kg IV q8h). Penicillin-allergic pts can receive TMP-SMZ (15/75 mg/kg IV daily in 3 divided doses). Therapy for meningitis in an immunocompetent pt should continue for 2–3 weeks following defervescence. Immunosuppressed pts should probably receive 4–6 weeks of therapy. Listeriosis in pregnancy is treated with ampicillin (1–1.5 g IV q6h for 2 weeks); erythromycin may be used as an alternative in the penicillin-allergic pt during the last month of pregnancy. Treatment of maternal bacteremia during pregnancy can prevent neonatal infection. For neonatal listeriosis, treatment consists of a 2-week course of ampicillin. In infants weighing <2000 g, the dose is 100 mg/kg daily in 2 divided doses during the first week of life and 150 mg/kg daily during the second week. Infants weighing ³2000 g should receive 150 (mg/ kg)/d in 3 equal doses during the first week of life and 200 (mg/kg)/d during the second week. Gentamicin can be added for neonatal listeriosis at 5 mg/ kg daily in 2 divided doses during the first week of life and 7.5 (mg/kg)/d in 3 divided doses during the second week.

PREVENTION   Prevention of listeriosis requires dietary counseling of those at high risk of disease and measures to reduce the contamination of food sources.

For a more detailed discussion, see Munford RS: Meningococcal Infections, Chap. 146, p. 927; and Schuchat A, Broome CV: Infections Caused by Listeria monocytogenes, Chap. 142, p. 915, in HPIM-15.



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