She felt very tired Dolly was doing well in her first year at university when sh

Question

She felt very tired Dolly was doing well in her first year at university when she developed a cough and diarrhea o bed early in her dormitory room. The next morning she woke early with a severe firmary headache. She felt sick and her neck seemed to be stiff. Her roommate took her to the university itn emergency room. She seemed ill and somewhat confused to the nurse on duty, wh o found that Dolly had a blood pressure of 70:40 (low), a pulse of 124 (fast), a respiratory rate of 24 (increased) and a temperature 39 2°C (elevated). The nurse noticed a petechial rash (small areas of reddish-purple discoloration) on chest and urgently summoned the physician on call, Dr. Tolstoy. He found that Dolly had a red moderate enlargement of the tonsils. No other physical symptoms were apparent except for the neck and the petechial rash on her palate, trunk, and extremities. Dr. Tolstoy immediately placed an intravenous needle into a vein on the back of Dolly's left hand, obtained blood for blood counts and bacterial cultures started intravenous administration of the antibiotic Cephtriaxone because he suspected meningococcal meningitis. He then performed a lumbar puncture to obtain cerebrospinal fluid (CSF). The blood cultures grevw piratory rate of 24 (increased) and a temperature of stiffness and eisseria meningitidis (meningococcus) serogroup C. The CSF proved sterile but contained 20 white blood cells j.tr (an abnormally high number; CSF usually contains five or fewer white blood cells pl. Dolly's hematocrit was 36.5% (slightly low) and her blood white-cell count was 8700 cells 11, of which 90% were neutrophils and 10% were lymphocytes Dolly quickly improved on continued intravenous antibiotic therapy The fever disappeared, she became alert, and her neck stiffness resolved over the next 72 hours. Blood taken after 24 hours of antibiotic treatment proved sterile on culture and she was discharged from the infirmary Dolly told Dr Tolstoy that she had meningococcal meningitis in her third year of high school. She was told at the time that she had positive CSF and blood cultures for N. Meningitidis serogroup Y. Dr. Tolstoy suspected that Dolly might have a complement deficiency What would Dr. Tolstoy do to confirm that there was a complement deficiency? Why do you think a complement deficiency would cause meningococcal meningitis infections? Outline three mechanisms that might explain the etiology Which complement component deficiency might prove to be the most devastating?

Explanation / Answer

1. Complement defieciency is immunodeficiency of absent or suboptimal functioning of one of the complement system proteins. Hypocomplementemia may be used more generally to refer to decreased complement levels. Among the diagnostic tests that can be done in determining if an individual has complement deficiencies

a. CH50 measurement

b. Immunochemical methods

c. C3 deficiency screening

d. Mannose binding lectin

e. Plasma levels

2. The importance of complement mediated bactericidal activity in protection against meningococcal disease is also underscored by the high incidence of invasive meningococcal disease in persons with terminal complement deficiencies. The requirement for protection through membrane attack complex appears to be unique for Neisseria meningitidis and for disseminated gonococcal infections, terminal complement deficient patients are not at a greater risk for contracting other gram negative infections. Considerable evidence supports the notion that the complement system plays a unique role in prevention of meningococcal disease, the clinical manifestations of this disease and its outcome. These include

a. The inverse correlation between complement dependent bactericidal activity and the age related incidence of meningococcal disease in general population.

b. The fact that approximately 80% of all identified systemic bacterial infections occurring in complement deficienct individuals are caused by meningococci

c. The direct correlation between the extent of complement activation, the concentration of circulating meningococcal endotoxin.

3. C3 is the most abundant and most critical of the complement proteins, essential for activation through all pathways. It is therfore not surprising that total C3 deficiency, a very rare finding restricted to a few dozen families is devastating.

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