Systemic meningococcal infection and complement deficiency

To The Editors: A previously healthy 17-year-old African-American young man was transferred to Hackensack (NJ) University Medical Center for evaluation and management of fever and purpuric rash compatible with meningococcemia. Blood cultures grew Neisseria meningitidis serogroup Y, and he was treated with intravenous ceftriaxone for 10 days. A total hemolytic complement (CH50) screening assay was abnormal (<10 complement activation EIA units) at discharge. Levels of individual complement components C3, C4, C5, C7, C8 and C9 were normal. However, C6 was undetectable with no precipitin ring identified by radioimmunodiffusion methodology. Polysaccharide meningococcal quadrivalent (A, C, Y, W-135) vaccine was administered, and education regarding febrile illnesses was provided. A letter addressing the management of febrile episodes for health care providers was given to the patient’s parents and pediatrician. Family history was unremarkable, and the patient’s mother, father and 14-year-old sister were screened with CH50 assays. His parents’ screening CH50 assays were normal, but his sister’s CH50 assay was abnormal, and her C6 was undetectable. Her past history was unremarkable, meningococcal vaccine was administered, education was provided, and a letter outlining management of fever given. The family was referred for genetic counseling. Meningococcal disease occurs in 50 to 60% of homozygous affected individuals with late complement component deficiencies of C5, C6, C7, C8 or C9, which are critical in supporting complement-dependent bactericidal activity against Neisseria spp. 1 Ellison et al. 2 identified congenital complement deficiencies in 3 (15%) of 20 patients evaluated for their first serious meningococcal infection. We prospectively determined a complement deficiency prevalence rate of 18% in a series of pediatric patients from Long Island with their first episode of systemic meningococcal infection. 3 The current patient reinforces the recommendation to perform a screening test (CH50 assay) for complement function in all patients with their first episode of systemic meningococcal or gonococcal infection. 4 It is important to identify these patients for a number of reasons. Education of parents and health care professionals with regard to febrile illnesses is of highest priority. Febrile episodes in these patients warrant evaluation by a physician who is aware of the patient’s complement deficiency and empiric antimicrobial therapy where indicated after blood and other appropriate cultures are obtained. Administration of the quadrivalent meningococcal vaccine may reduce the risk of meningococcal disease in affected individuals by enhancing the opsonophagocytic elimination of these organisms. The role of continuous antimicrobial prophylaxis in the management of these patients remains to be delineated. Because late complement component deficiencies are genetically determined by autosomal recessive transmission, genetic counseling is also indicated. Robert J. Leggiadro, M.D.