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.

Peripheral blood cell-specific cytokines in persons with untreated HIV infection in Malawi, Africa.

Human immunodeficiency virus (HIV) infection is the primary cause of morbidity and mortality in Malawi, Africa, because of its many effects on the immune system. Immune cells communicate through cytokines; therefore, we examined the relationships between HIV serostatus and cell-specific cytokine production for 40 asymptomatic, employed adults and 312 acutely ill, hospitalized patients in Malawi. We also measured the plasma HIV-1 RNA levels of 13 asymptomatic persons and 83 patients found to be HIV(+). We incubated peripheral whole blood with brefeldin-A +/- phorbol 12-myristate 13-acetate and ionomycin and then permeabilized, fixed, fluorescently stained, and examined the mononuclear cells with four-color, six-parameter flow cytometry. The percentage of lymphocytes expressing CD4 did not differ significantly between the HIV(+) and HIV(-) healthy adults (medians, 35.2 vs. 40.8%, respectively), but a wide array of cytokine parameters were lower in the HIV(+) than in the HIV(-) asymptomatic persons, for example, median percentages of T cells producing induced interleukin 2 (IL-2) (8.7 vs. 16.5%, respectively) and spontaneously producing IL-6 (0.7 vs. 11.0%, respectively). Also, four T cell parameters reflecting type 2-to-type 1 cytokine balances (T2/T1) were higher in the HIV(+), versus HIV(-), asymptomatic persons. Unlike the healthy adults, for patients with mycobacteremia/fungemia or malaria, the HIV(+) patients had higher median percentages of T cells and CD8(+) T cells producing induced interferon gamma than did the HIV(-) PATIENTS: For both asymptomatic and acutely ill persons, HIV-1 plasma levels were positively correlated with T2/T1 parameters. Cell-specific cytokine effects of HIV infection may precede measurable effects on CD4 expression. Cytokine therapies, even beyond periodic administration of IL-2, may improve the responses of HIV-infected persons to both HIV and coinfections.

Clinical and immune impact of Mycobacterium bovis BCG vaccination scarring.

The World Health Organization recommends Mycobacterium bovis BCG vaccination in areas of high tuberculosis prevalence. BCG's clinical and immune effects, not necessarily Mycobacterium tuberculosis specific, are unclear. BCG vaccine scarring often is used as a surrogate marker of vaccination or of effective vaccination. We evaluated BCG scarring status in relation to clinical findings and outcome in 700 hospitalized Malawians, of whom 32 had M. tuberculosis bloodstream infections (BSI) (10 of whom had cellular immune studies done) and of whom 48 were infants <6 months old and therefore recently vaccinated (19 of whom had immune studies). In the patients >/=6 months old, scarring was not related to the presence of pulmonary symptoms (35 versus 30%), chronic cough or fever, mortality, or M. tuberculosis BSI. In M. tuberculosis BSI patients, scarring was unrelated to mortality, vital signs, or clinical symptoms but those with scarring had higher proportions of memory and activated T cells and more type 2-skewed cytokine profiles. Infants with either BCG scarring (n = 10) or BCG lesional inflammation (n = 5) had no symptoms of sepsis, but 18 of 33 infants without BCG vaccination lesions did. Those with BCG lesions had localized infections more often than did those without BCG lesions. These infants also had lower median percentages of lymphocytes spontaneously making interleukin-4 (IL-4) or tumor necrosis factor alpha (TNF-alpha) and lower ratios of T cells spontaneously making IL-4 to T cells making IL-6. Thus, we found that, in older patients, BCG vaccine scarring was not associated with M. tuberculosis-specific or nonspecific clinical protection. Those with M. tuberculosis BSI and scarring had immune findings suggesting previous M. tuberculosis antigen exposure and induction of a type 2 cytokine pattern with acute reexposure. It is unlikely that this type 2 pattern would be protective against mycobacteria, which require a type 1 response for effective containment. In infants <6 months old, recent BCG vaccination was associated with a non-M. tuberculosis-specific, anti-inflammatory cytokine profile. That the vaccinated infants had a greater frequency of localized infections and lesser frequency of sepsis symptoms suggests that this postvaccination cytokine pattern may provide some non-M. tuberculosis-specific clinical benefits.