Meningococcemia: Heading Off a Killer
Warren B. Howe, MD
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In Brief: Meningococcemia is a dangerous disease requiring early and aggressive treatment to prevent a potentially lethal outcome. It often occurs in relatively closed groups, including sports camps and athletic teams. A high index of suspicion must be maintained when evaluating acute febrile illness, particularly in people younger than 20. Treatment includes antibiotics and intensive care support. Prophylaxis in the intimately exposed population, and education about signs and symptoms of the disease for more peripheral contacts are critical for successfully limiting any outbreak.
The youngster looked ill. He was attending a summer sports camp and woke the trainer at 5:00 am to report feeling hot and having nausea and abdominal pain. The trainer alertly notified the camp physician, who saw the 10-year-old boy shortly thereafter and noted an ill-appearing patient with a temperature of 103°F, diffuse abdominal tenderness, and a 1.5-cm tender, ecchymotic lesion on his left lateral malleolus. He did not have signs of meningitis.
By the time the patient was transferred to the hospital, he had developed a number of petechial lesions on his limbs and trunk. Antibiotic treatment for septicemia was instituted, and the boy made an excellent recovery. Blood cultures later grew Neisseria meningitidis.
Almost simultaneously with the patient's hospital admission, a friend of the patient—with whom the patient had attended a swim meet 2 days before departing to camp—was admitted to the same hospital with similar symptoms. This second 10-year-old boy was also successfully treated for meningococcemia. As is usually the case in outbreaks of invasive meningococcal disease, the camp administration and the parents of children attending the camp were considerably dismayed about the implications of this infection. The camp physician spent more effort in arranging prophylaxis for those exposed and educating the entire population involved about the disease than was spent in treating the index case.
No further cases occurred. The successful outcome, achieved without significantly interrupting the camp's activities, was satisfying for all concerned.
Outbreaks of meningococcal disease occur sporadically and may, as in this case report, involve athletes and sports situations. This is a dangerous disease that demands early and aggressive treatment, vigorous measures to control spread, and reassurance for the larger population that may feel threatened by the outbreak.
Neisseria meningitidis is a gram-negative diplococcus whose reservoir is the human nasopharynx. Serogroup A is associated with large-scale epidemics, particularly in developing countries, while serogroups B and, increasingly, C are currently associated with localized outbreaks in North America. Jackson et al (1) have documented 21 outbreaks of serogroup C disease in the United States between 1981 and 1993, with dramatically increasing frequency since 1990. The emergence of new, increasingly virulent strains has also been associated with outbreaks (1,2).
The organism can be cultured in 5% to 15% of healthy people and spreads when people inhale droplets of contaminated upper-respiratory secretions. During outbreaks, this percentage rises significantly in the affected population, although only a small number of those carrying the organism will develop clinical meningococcal disease. The incubation period is 1 to 10 days, usually 4 days or less.
Most cases of invasive meningococcal disease occur in patients younger than 20, and the risk of contagion seems to vary with the closeness and persistence of contact; it is highest in household members. Outbreaks have been reported in populations in other relatively closed settings, such as military camps, day care centers, and colleges. However, many patients cannot recall exposure to symptomatic individuals.
Signs and Symptoms
Few, if any, symptoms attend nasopharyngeal infection by meningococci. In the early stages of invasive disease, meningococcemia usually presents as an acute febrile illness with malaise, nausea, myalgia or arthralgia, significant fever, and chills. Instead of the rapid resolution of symptoms usually associated with self-limited infections, the patient with meningococcemia usually becomes progressively and impressively sicker with toxemia and prostration.
Rash occurs in most patients, and because it can develop very quickly, should be searched for repeatedly. It is initially macular, erythematous, and located mainly on the extremities; petechiae and purpura subsequently develop. Other symptoms depend on where the meningococci localize after hematogenous spread.
Meningitis, with symptoms such as a stiff neck, severe headache, back pain, and mental status changes, is the most common localized manifestation. Meningococcal pneumonia, endocarditis, myocarditis, pericarditis, pleurisy, peritonitis, and arthritis may also occur. Approximately 10% of patients with meningococcemia develop Waterhouse-Friderichsen syndrome, characterized by a fulminant septicemia with shock, widespread purpura (purpura fulminans), congestive heart failure, and progressive, usually irreversible, collapse.
Laboratory abnormalities typically include significant leukocytosis with left shift, but leukopenia may occur in overwhelming disease. Coagulopathy may be demonstrable. If meningeal infection has occurred, purulent spinal fluid is encountered with elevated cerebrospinal fluid protein and decreased glucose. Cultures of blood and cerebrospinal fluid will usually be positive for meningococci; serogroup and serotype identification can aid epidemiologic investigation (1).
The key to effective intervention is a high index of suspicion at the early stage, particularly during periods of increased respiratory disease in the community, since meningococcemia also seems to peak at such times. Once meningococcemia is suspected, antibacterial treatment must be instituted promptly, because early treatment seems to improve prognosis (3). Urgent hospitalization for intensive care and support is mandatory.
Blood cultures can be obtained as the intravenous (IV) line is being placed. For adults, IV penicillin G, 2 million units every 2 hours around the clock, is appropriate. The dose for children is 250,000 units/kg/day administered every 2 hours in divided doses.
If penicillin-resistant meningococci are suspected, alternatives include IV ceftriaxone sodium (adults 4 g/day, children 100 mg/kg/day; doses every 12 hours) or chloramphenicol (adults and children 100 mg/kg/day, maximum 4 g/day; doses every 6 hours). Ceftriaxone is preferred as initial therapy in children, because septicemia with Haemophilus influenzae can produce a clinical picture similar to that of meningococcemia. Chloramphenicol is especially useful in patients who have a history of anaphylactic reaction to penicillin; its use is otherwise limited by potential hematologic toxicity.
Avoiding an Epidemic
Preventing the spread of the disease and treating new cases early are critical. This is an urgently reportable disease in all states. Once the diagnosis is made, the early symptoms of meningococcemia should be widely publicized, and people in the potentially exposed population should be urged to seek immediate medical evaluation if they contract a febrile illness.
Patients who have meningococcemia should be isolated during the first 24 to 36 hours of antibacterial therapy. Household members are at greatest risk for contagion, followed by contacts within the relatively closed populations mentioned earlier. People in close contact with the patient should receive chemoprophylaxis aimed at eradicating meningococci from the nasopharynx. More peripheral contacts are not routinely treated, although I have adopted the philosophy of treating any peripheral contact who requests prophylaxis.
Currently recommended medications for prophylaxis include the drug of choice, rifampin, and also minocycline, ceftriaxone, ciprofloxacin, and—when the organism is known to be sensitive to it—sulfadiazine (table 1). Remember that rifampin stains body fluids orange, including tears, so permanent staining of soft contact lenses can result. Because meningococci can often be recovered from the nasopharynx of treated meningococcemia patients, they must also receive chemoprophylaxis before being discharged from the hospital (5).
______________________________________________________________________________ Table 1. Meningococcal Disease Chemoprophylaxis for Children and Adults ______________________________________________________________________________ Drug Dosage Dosage Adult, Child Dosage Child 13 Yr or Older Child 1-12 Yr Under 1 Yr Comments ______________________________________________________________________________ Rifampin 600 mg orally 10 mg/kg 5 mg/kg orally Preferred every 12 hr, (max 600 mg) every 12 hr, drug 4 doses orally every 12 4 doses hr, 4 doses Sulfadiazine 1,000 mg 500 mg orally 500 mg orally Only if index orally every every 12 hr, every 24 hr, organism 12 hr, 4 doses 4 doses 2 doses sensitive to this drug Ciprofloxacin Age 18 yr NA NA Not recommended or older: 750 for under age mg as single 18 yr oral dose (4) Minocycline 200 mg orally Age 8 yr or NA Avoid in followed by older: 4 mg/kg pregnancy 6 100-mg oral orally followed and under doses every by 6 2-mg/kg age 8 yr 12 hr oral doses every 12 hr Ceftriaxone 250 mg, 125 mg, 125 mg, Intramuscular sodium single dose single dose single dose NA=Not applicable ______________________________________________________________________________
Meningococcal vaccine effective against serogroups A, C, Y, and W-135 (but not serogroup B) is available. It is used routinely in the military, and is recommended for travel to endemic areas. Patients who may have impaired resistance—such as those who have no spleen or are deficient in terminal-component complement—should be offered immunization. Universal immunization is not practiced, but the vaccine is recommended by some authorities as a supplement to chemoprophylaxis for controlling outbreaks involving a vaccine-sensitive organism (1).
By educating themselves about common manifestations of the disease, physicians can raise their index of suspicion for meningococcal disease in patients affected by febrile illness, which can result in early diagnosis. Then quick action can be taken to treat the afflicted person and help prevent the spread of the disease.
Dr Howe is the team physician at Western Washington University in Bellingham, Washington, and a member of the editorial board of The Physician and Sportsmedicine. Address letters to Warren B. Howe, MD, 4222 Northridge Way, Bellingham, WA 98226; e-mail to [email protected]