Predictors of immunity after a major serogroup W-135 meningococcal disease epidemic, Burkina Faso, 2002.

BACKGROUND: The African meningitis belt undergoes recurrent epidemics caused by Neisseria meningitidis serogroup A. During 2002, Burkina Faso documented the first large serogroup W-135 (NmW-135) meningococcal disease epidemic. To understand the emergence of NmW-135, we investigated meningococcal carriage and immunity. METHODS: Immediately after Burkina Faso's epidemic, we conducted a cross-sectional survey of meningococcal carriage and seroprevalence in an epidemic and a nonepidemic district. We identified predictors of elevated NmW-135 serum bactericidal activity (SBA), a functional correlate of protection, using multivariate logistic regression. RESULTS: The NmW-135 carriage rate was 25.2% in the epidemic district and 3.4% in the nonepidemic district (P<.0001). Compared with residents of the nonepidemic district, those of the epidemic district had higher geometric mean titers of NmW-135 SBA (P<.0001). NmW-135 SBA titers>or=1:8, an estimated protective threshold, were observed in 60.4% and 34.0% of residents of the epidemic and nonepidemic district, respectively (P=.0002). In a multivariate model, current NmW-135 carriage, age, and residence in the epidemic district were independent predictors of having an NmW-135 SBA titer>or=1:8. CONCLUSIONS: Extensive NmW-135 carriage and transmission in the epidemic area caused residents to acquire natural immunity. Serial carriage and seroprevalence surveys could establish the duration of immunity in the population. The persistent circulation of NmW-135 underscores the potential for periodic NmW-135 epidemics in Africa.

No evidence of a mild form of inhalational Bacillus anthracis infection during a bioterrorism-related inhalational anthrax outbreak in Washington, D.C., in 2001.

BACKGROUND: The mail-related dispersal of Bacillus anthracis spores in the Washington, D.C., area during October 2001 resulted in 5 confirmed cases of inhalational anthrax. We identified an additional 144 ill persons who were potentially exposed to aerosolized spores and whose symptoms were compatible with early inhalational anthrax but whose clinical course and nonserologic laboratory evaluation revealed no evidence for B. anthracis infection. We hypothesized that early antibiotic use could have decreased the sensitivity of diagnostic tests or that bioterrorism-related inhalational anthrax may include mild disease. METHODS: Eligible patients included those with illness compatible with early inhalational anthrax who had potential exposure to B. anthracis. Patient serum samples were tested for immunoglobulin G (IgG) antibody against B. anthracis protective antigen (PA) using a sensitive enzyme-linked immunosorbant assay (sensitivity, 97.6%). RESULTS: Of the 144 eligible patients, 66 (46%) had convalescent-phase serum samples available for testing; 29 (44%) worked in an area considered to pose a high risk of exposure to B. anthracis spores. Of the 37 patients who worked in areas that did not meet the definition of high-risk exposure, 23 (62%) worked in United States postal or other government facilities in which exposure was plausible but not documented. None of the 66 patients with convalescent-phase serum samples showed evidence of an anti-PA IgG serologic response to B. anthracis. CONCLUSIONS: These data suggest that a mild form of inhalational anthrax did not occur and that surveillance for moderate or severe illness was adequate to identify all inhalational anthrax cases resulting from the Washington, D.C., bioterrorism-related anthrax exposures.

Immune responses to Bacillus anthracis protective antigen in patients with bioterrorism-related cutaneous or inhalation anthrax.

Anti-protective antigen (PA) immunoglobulin (Ig) G, toxin neutralization, and PA-specific IgG memory B cell responses were studied in patients with bioterrorism-related cutaneous or inhalation anthrax and in a patient with laboratory-acquired cutaneous anthrax. Responses were determined for >1 year after the onset of symptoms. Eleven days after the onset of symptoms (15 days after likely exposure), anti-PA IgG was detected in 16 of 17 patients with confirmed or suspected clinical anthrax who were tested. Anti-PA IgG remained detectable 8-16 months after the onset of symptoms in all 6 survivors of inhalation anthrax and in 7 of 11 survivors of cutaneous anthrax who were tested. Anti-PA IgG levels and serum toxin neutralizing activity were strongly associated (R2=0.83). PA-specific IgG memory B cells were detectable in all 6 survivors of inhalation anthrax but in only 2 of 7 patients with cutaneous anthrax who were tested. Anti-PA IgG is an important diagnostic marker of anthrax, a predictor of serum anti-toxin activity, and a marker of immunological memory against anthrax.

Specificity of the antibody response to the pneumococcal polysaccharide and conjugate vaccines in human immunodeficiency virus-infected adults.

Nonspecific antibodies, which are thought to be nonprotective, have been shown to contribute a substantial proportion of the measured concentration in the standardized immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) for pneumococcal polysaccharide capsular antibodies. The presence of such antibodies in human immunodeficiency virus (HIV)-infected persons has not been evaluated. The amount of nonspecific antibodies is proportional to the reduction in IgG antibody concentration that occurs with serum absorption with the heterologous polysaccharide 22F. We measured the amount of nonspecific antibodies before and after vaccination with the pneumococcal conjugate vaccine (PCV; n = 33) or the pneumococcal polysaccharide vaccine (PPV; n = 34) in HIV-infected adults with CD4 counts of >/== 200 cells/mm3. Blood was drawn before and 2 months after vaccination. For prevaccination sera, we found a substantial amount of nonspecific antibodies for serotypes 4, 6B, 9V, and 23F (23 to 47% of measured IgG concentration), but not for serotype 14. There tended to be proportionately less nonspecific antibodies in postvaccine sera than prevaccine sera for PCV, but not for PPV. Subjects with a low HIV viral load (

Antibody responses in postsplenectomy trauma patients receiving the 23-valent pneumococcal polysaccharide vaccine at 14 versus 28 days postoperatively.

BACKGROUND: We have previously demonstrated, using functional antibody assays, that patients undergoing splenectomy for trauma exhibit a better response to pneumococcal immunization when vaccinated at 14 days postoperatively versus 1 or 7 days. However, patients immunized at 14 days failed to reach the response of normal controls. This study was conducted to determine whether even later immunization would improve the antibody response. METHODS: Forty surviving patients undergoing emergent splenectomy were randomized to receive Pneumovax at 14 or 28 days after splenectomy. Blood samples were drawn at the time of vaccination (prevaccination) and 4 weeks later (postvaccination). A control group of 24 healthy adults was used for comparison. Antibody titers to four of the most common serotypes were determined by enzyme-linked immunosorbent assay and opsonophagocytic assay (OPA). RESULTS: Samples from 38 patient were analyzed. Each serotype and each group tested demonstrated a statistically significant increase in geometric mean enzyme-linked immunosorbent assay immunoglobulin G antibody concentration (microg/mL) and OPA titer (1/dilution) after vaccination. There were no statistically significant differences (p >or= 0.07) in the immunoglobulin G antibody concentrations and OPA titers between the 14-day or the 28-day study groups when compared with normal healthy adults regardless of the serotype tested. In addition, there were no differences in the antibody responses between the 14-day and the 28-day study groups. CONCLUSION: Despite our previous study suggesting that delay in vaccination after emergent splenectomy resulted in improved antibody response, antibody response was not improved any further by delaying vaccination to 28 days.

Specific, sensitive, and quantitative enzyme-linked immunosorbent assay for human immunoglobulin G antibodies to anthrax toxin protective antigen.

The bioterrorism-associated human anthrax epidemic in the fall of 2001 highlighted the need for a sensitive, reproducible, and specific laboratory test for the confirmatory diagnosis of human anthrax. The Centers for Disease Control and Prevention developed, optimized, and rapidly qualified an enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) antibodies to Bacillus anthracis protective antigen (PA) in human serum. The qualified ELISA had a minimum detection limit of 0.06 micro g/mL, a reliable lower limit of detection of 0.09 micro g/mL, and a lower limit of quantification in undiluted serum specimens of 3.0 micro g/mL anti-PA IgG. The diagnostic sensitivity of the assay was 97.8%, and the diagnostic specificity was 97.6%. A competitive inhibition anti-PA IgG ELISA was also developed to enhance diagnostic specificity to 100%. The anti-PA ELISAs proved valuable for the confirmation of cases of cutaneous and inhalational anthrax and evaluation of patients in whom the diagnosis of anthrax was being considered.

Viral load response to a pneumococcal conjugate vaccine, polysaccharide vaccine or placebo among HIV-infected patients.

We determined the HIV viral load in 66 adults randomly assigned to receive pneumococcal immunization with one or two doses of protein conjugate vaccine, one dose of polysaccharide vaccine, one dose of each, or placebo. Second doses were given 8 weeks after the first. Mean baseline viral load and CD4 cell count were 3.41 copies/ml (log10) and 457 cells/microl, respectively. We found no change in viral load during 24 weeks of follow-up for any vaccine or combination of vaccines or placebo.

Assignment of additional anticapsular antibody concentrations to the Neisseria meningitidis group A, C, Y, and W-135 meningococcal standard reference serum CDC1992.

We assigned additional enzyme-linked immunosorbent assay antibody concentrations (immunoglobulin G [IgG], IgM, and IgA, and total) to the Neisseria meningitidis standard reference serum CDC1992 for groups Y and W-135 to 12 Centers for Disease Control and Prevention quality control sera. These assignments will supplement previous assignments and will aid in the evaluation of present and developing vaccines.