Ablation of cyclooxygenase-2 in forebrain neurons is neuroprotective and dampens brain inflammation after status epilepticus.

Cyclooxygenase-2 (COX-2), a source of inflammatory mediators and a multifunctional neuronal modulator, is rapidly induced in select populations of cortical neurons after status epilepticus. The consequences of rapid activity-triggered induction of COX-2 in neurons have been the subject of much study and speculation. To address this issue directly, we created a mouse in which COX-2 is conditionally ablated in selected forebrain neurons. Results following pilocarpine-induced status epilepticus indicate that neuronal COX-2 promotes early neuroprotection and then delayed neurodegeneration of CA1 pyramidal neurons, promotes neurodegeneration of nearby somatostatin interneurons in the CA1 stratum oriens and dentate hilus (which themselves do not express COX-2), intensifies a broad inflammatory reaction involving numerous cytokines and other inflammatory mediators in the hippocampus, and is essential for development of a leaky blood-brain barrier after seizures. These findings point to a profound role of seizure-induced neuronal COX-2 expression in neuropathologies that accompany epileptogenesis.

Progress toward control of rubella and prevention of congenital rubella syndrome--worldwide, 2009.

Rubella, usually a mild rash illness in children and adults, can cause serious consequences when a pregnant woman is infected, particularly in early pregnancy. These serious consequences include miscarriage, fetal death or an infant born with birth defects (i.e., congenital rubella syndrome (CRS)). The primary purpose for rubella vaccination is the prevention of congenital rubella infection including CRS. Since 1969, several rubella virus vaccines have been licensed for use; however, until the 1990s, use of rubella-containing vaccine (RCV) was limited primarily to developed countries. In 1996, it was estimated that 110,000 infants with CRS were born annually in developing countries. In 2000, the first World Health Organization rubella vaccine position paper was published to guide introduction of RCV in national childhood immunization schedules. From 1996 to 2009, the number of countries that introduced RCV into their national routine childhood immunization programs increased by 57% from 83 countries in 1996 to 130 countries in 2009. In addition, three of the six WHO regions established rubella control and CRS prevention goals: Region of the Americas and Europe rubella elimination by 2010 and 2015, respectively, and Western Pacific Region-accelerated rubella control and CRS prevention by 2015. Also, during this time period, the number of rubella cases reported decreased from 670,894 in 2000 to 121,344 in 2009. Rubella control and prevention of CRS can be accelerated by integrating with current global measles mortality reduction and regional elimination activities.

Mumps transmission in hospitals.

Although sporadic transmission of mumps within hospitals to patients and staff is well documented, outbreaks of mumps within hospitals have only rarely been reported. The widespread mumps outbreaks that occurred in Tennessee in 1986-1987 provided an opportunity to assess the extent of the problems caused by mumps in hospitals. Information was obtained from 146 (95%) of 154 infection control practitioners in the state. Infection control problems caused by mumps were reported from 17 (12%) of 146 hospitals. The 17 hospitals in which these incidents occurred were located in counties that accounted for 67% of the reported mumps cases statewide during this period. Although most cases of mumps in health care workers were community-acquired, six health care workers in three different hospitals developed mumps following nosocomial exposure. In two institutions, nine patients contracted mumps while hospitalized. Both were long-term-care facilities housing adolescents, who had substantial contact with a community where mumps outbreaks were ongoing. This study suggests that mumps poses a small but real risk to both patients and staff in hospitals, particularly in long-term-care facilities caring for adolescents and young adults. In communities where mumps activity is ongoing, hospitals should consider identifying potentially susceptible staff members at risk for infection and offering vaccine. Likewise, susceptible patients in long-term-care facilities should be immunized.

Overview of policies affecting vaccine use in child day care.

Vaccination policies for preschool-age children, including those in child day care, have undergone frequent changes within the past several years in response to the development of new vaccines (DTaP, Hib conjugate vaccines), the changing epidemiology of vaccine-preventable diseases (measles), and the establishment of new objectives for the control and elimination of vaccine-preventable diseases (Hib, hepatitis B). The acquisition and spread of vaccine-preventable diseases can be minimized in child day-care settings by vaccinating all children, establishing a continuing system by which all children remain fully vaccinated on schedule, providing educational materials to parents about the recommended schedule of routine childhood vaccines, and implementing new recommendations for vaccine use.

Childhood upper respiratory tract infections: to what degree is incidence affected by day-care attendance?

Risk factors for acute upper respiratory tract disease in childhood were evaluated in a population-based sample of the Atlanta metropolitan area. Mothers from 449 households containing 575 children less than 5 years of age were selected by random-digit dialing and questioned about upper respiratory tract infection and ear infection occurring in their children during the preceding 2 weeks. Household demographic and socioeconomic characteristics, maternal smoking history and child day-care attendance and breast-feeding information were also obtained. For children less than 5 years of age, the reported incidence of upper respiratory tract infection was 24%, and of ear infection, 6%. Controlling for the other variables measured, day-care attendance was associated with a significantly increased risk of both illnesses. For upper respiratory tract infection, increased risk was present for all children attending day care (P = .02, odds ratio = 1.6), whereas for ear infection, risk could be demonstrated only for full-time attendees (P = .005, odds ratio = 3.8). Maternal smoking was a second independent risk factor for a child's having upper respiratory tract infection (odds ratio = 1.7, P = .01). Thirty-one percent of all upper respiratory tract infection among day-care attendees and 66% of all ear infections among full-time day-care attendees were attributable to day-care attendance. Given the proportion of children in day care, 9% to 14% of the total burden of upper respiratory tract disease in this population was day care related.(ABSTRACT TRUNCATED AT 250 WORDS)

Changing epidemiology of mumps and its impact on university campuses.

The reported incidence of mumps has declined dramatically since licensure of the live attenuated mumps vaccine in the United States in 1967, particularly in young children. Because administration of the vaccine was not widely practiced during the first decade it was available, there is now a cohort of teenagers and young adults who are relatively underimmunized. Reported mumps cases in this cohort increased substantially during 1986 to 1987. Mumps outbreaks at three Illinois universities, from which 123 clinical cases were reported between September 1986 and May 1987, were investigated. Meningeal involvement was reported in 17% of case-patients, orchitis occurred in 19% of 64 men, 6% of patients were hospitalized, and direct health care costs were estimated at $264 per case and more than $32,000 for the three outbreaks combined. The risk of mumps illness was greater for students less than 20 years of age (relative risk [RR] = 2.1, 95% confidence interval [CI] = 1.4, 3.1); students residing in dormitories (RR = 2.7, 95% CI = 1.6, 4.6); and out-of-state students (RR = 1.8, 95% CI = 1.0, 3.0). Because the available data suggest that mumps in college-aged persons is due chiefly to a failure to vaccinate susceptible persons, colleges and universities should become one major focus of mumps prevention activities to reduce susceptibility in this high-risk population.

Plasma viremia titration and RNA quantitation in ICD-p24 negative HIV type-1-infected patients.

Quantitative culture of human immunodeficiency virus (HIV) was performed on 202 plasma samples obtained from asymptomatic and early symptomatic HIV-1 infected patients (mean CD4+ count: 186/mm3) before antiretroviral therapy was started. HIV could be isolated from 84% of the plasma samples (titers ranging from 10(0) to 10(2.75) TCID50/ml). Immune complex dissociated p24 antigen (ICD-p24) was detected in 66% of the samples. Only 23 samples (11%) were negative for both ICD-p24 as well as HIV culture. Discordant results were obtained in 55 samples, and 45 samples negative for ICD-p24 were positive for HIV culture. A significant proportion (42%) of patients that were negative for ICD-p24 belonged to a very advanced group with very low CD4+ cell count. However, almost 90% of these ICD-p24 negative samples were positive for HIV plasma viremia, stressing the value of this virological marker in patients with low CD4+ cell count and without any detectable ICD-p24 antigenemia. HIV-1 RNA was detected in all ICD-p24 negative plasma samples tested by the branched DNA (bDNA) assay. A very good correlation was found between high RNA copy number and HIV plasma isolation in samples obtained from patients with low CD4+ cell count, suggesting that HIV-1 RNA quantitation may also reflect viral infectivity of plasma.

Control of epidemic group A meningococcal meningitis in Nepal.

During the first six months of 1983, an epidemic of serogroup A meningococcal meningitis occurred in the Kathmandu valley of Nepal, resulting in 875 cases and 95 deaths. The annual attack rate was 103 cases per 100,000 population, with a peak attack rate occurring in April. Epidemic meningococcal disease had not been recognized previously in Nepal. Early in 1984, a review of hospital-based data on pyogenic meningitis in Kathmandu showed three times as many cases per month compared with the same period the previous year, suggesting that a recurrent epidemic was unfolding. Beginning in February 1984, a vaccination campaign directed at a high-risk target population of people aged 1-24 years was launched; over 329,000 doses of bivalent A/C meningococcal vaccine were given, achieving approximately 64% coverage of the target population. A dramatic decline in the number of new meningitis cases occurred coincident with the initiation of the mass vaccination campaign. This experience demonstrates that it is possible, with appropriate surveillance efforts, to detect an evolving epidemic of meningococcal disease early in its course and to institute control measures in advance of the expected epidemic peak.

Defining surrogate serologic tests with respect to predicting protective vaccine efficacy: poliovirus vaccination.

Inactivated and trivalent oral poliovirus vaccines contain either formalin-inactivated or live, attenuated poliovirus, respectively, of the three serotypes. Interference among the three attenuated poliovirus serotypes was minimized with a "balanced-formulation" vaccine, and serologic responses after IPV were optimized by adjusting the antigenic content of each inactivated poliovirus serotype. Seroconversion is dependent on both the relative content as well as the absolute quantity of virus in the vaccine. The "gold standard" method to assess humoral antibody responses following vaccination is the neutralization assay. Any detectable titer of neutralizing antibody against poliovirus is considered protective against clinical paralytic diseases. Recently, standard procedures were adopted for conducting neutralization assays. Efforts are being undertaken now to develop a combined diphtheria and tetanus toxoids and pertussis vaccine and IPV vaccine in the United States using a dual-chambered syringe that mixes the content of both vaccines at the time of injection; this approach is necessary to overcome the potential detrimental effect of thimerosal on IPV (the preservative in DTP). Other vaccines that combine DTP and/or Haemophilus influenzae type b and/or hepatitis B with IPV appear feasible but require further investigation. New combination vaccines should induce similar or superior levels of neutralizing antibody in serum for individual protection against paralytic disease and mucosal immunity that effectively decreases viral replication in the intestine and pharynx for population protection against transmission of poliovirus.

Potential impact on vaccination coverage levels by administering vaccines simultaneously and reducing dropout rates.

BACKGROUND: Retrospective immunization coverage surveys conducted during 1991 and 1992 demonstrated that coverage levels for the routine childhood vaccines by 24 months of age in selected urban areas of the United States ranged from 10% to 52%, far below the US Public Health Service goal of 90%. Therefore, appropriate programmatic changes must be identified and incorporated. METHODS: We analyzed coverage survey data collected from 21 sites to measure the potential impact on coverage levels of implementing selected changes in vaccination practices. In a multistaged cluster survey design, school health records of kindergarten or first-grade students were randomly selected and dates of vaccination assessed. We evaluated changes in the vaccination practices, such as eliminating missed opportunities for simultaneous administration of vaccines and ensuring that children initiated the vaccination series on time (ie, by 3 months of age). We then calculated potential increases in coverage levels for a best-case scenario. RESULTS: From 77% to 96% of all children in the 21 sites had received at least one vaccination by their first birthday. Children were 2.3 to 17 times more likely to be up to date on their vaccinations by 24 months of age if they were up to date at 3 months of age. Each child had many opportunities for the simultaneous administration of diphtheria and tetanus toxoids and pertussis (DTP) vaccine, oral polio vaccine (OPV), and measles-mumps-rubella (MMR) vaccine that, if used appropriately, could have potentially raised coverage levels by 12% to 22% (median, 17%). The highest coverage levels could have been attained if all children had started the series on time and if advantage had been taken of all opportunities for simultaneous vaccination. Coverage levels for four doses of DTP vaccine, three doses of OPV, and one dose of MMR vaccine would have increased from a baseline of 10% to 52% to levels of 54% to 83%. CONCLUSIONS: Although the majority of children received a vaccination by their first birthday, the coverage level at 24 months of age was low. Tracking systems are needed to ensure that children do not drop out of the system once they have begun the vaccination series. In addition, all children who are late in beginning their vaccination series are at increased risk of not completing the recommended vaccination series on time, and these children need intensive follow-up and recall efforts. Also, providers need to administer all needed vaccines simultaneously.

Completeness of reporting for paralytic poliomyelitis, United States, 1980 through 1991. Implications for estimating the risk of vaccine-associated disease.

BACKGROUND: Although the risk of vaccine-associated paralytic poliomyelitis (VAPP) has remained relatively constant during the past 30 years, estimates of VAPP depend largely on the completeness of reporting to the existing passive surveillance system. The National Vaccine Injury Compensation Program constitutes an alternative system for reporting VAPP, and data available from this system permitted us to evaluate the completeness of the national poliomyelitis surveillance system. METHODS: We compared cases of paralytic poliomyelitis reported to the national surveillance system (maintained by the Centers for Disease Control and Prevention, Atlanta, Ga) with cases recommended for compensation by the National Vaccine Injury Compensation Program, Rockville, Md, and we calculated the observed completeness of reporting to the national system for 1980 through 1991. A capture-recapture method was also used to estimate completeness of reporting, ie, to account for cases potentially missed by both systems. In addition, we reviewed the epidemiology and updated the risk of VAPP based on the most current information on cases of VAPP. RESULTS: From 1980 through 1991, 105 cases of paralytic poliomyelitis were identified by the Centers for Disease Control and Prevention and National Vaccine Injury Compensation Program systems, 98 (93%) of which were VAPP (average, 8.2 cases per year). The observed completeness of reporting to the Centers for Disease Control and Prevention was 94%, and the estimated completeness of reporting (capture-recapture method) was 81%. The overall risk of VAPP was one case per 2.5 million doses of oral poliovirus vaccine distributed. In the sensitivity analysis, the risk estimates of VAPP remained relatively stable throughout a wide range of assumptions regarding underreporting and specificity of the case definition for paralytic poliomyelitis. CONCLUSION: The risk of VAPP remains virtually unchanged from previous estimates despite the inclusion of previously unidentified VAPP cases. Despite the potential for both underreporting and misclassification of cases, our risk estimates were relatively insensitive to either of these biases. Since both of these biases were in opposite directions, and both probably occurred with low frequency, the risk estimates provided in this report appear valid and approximate the "true" risk of VAPP in the United States.

Measles, mumps, and rubella vaccines.

With widespread use of the live virus vaccines for measles, mumps, and rubella, there has been a dramatic decrease in the incidence of all three diseases. At the same time, an increasing proportion of the remaining cases are occurring in adolescents and adults. Thus, vaccinations for these three diseases of childhood must be included in a comprehensive program for adult immunization. The vaccines have a proven history of safety and efficacy and are usually administered together as combined measles-mumps-rubella (MMR) vaccine. Vaccination for measles, mumps, and rubella is particularly important for susceptible adults likely to come in contact with infected children. Adults at particularly high risk for exposure may include daycare center workers, teachers and other school employees, college students, medical personnel, and those planning to travel outside the United States.

Poliomyelitis eradication: progress, challenges for the end game, and preparation for the post-eradication era.

In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally by the year 2000. Dramatic progress toward this goal has occurred: three of the six WHO regions (Region of the Americas, European Region, and Western Pacific Region) are now polio free; and the number of polio-endemic countries decreased from over 125 in 1988 to 30 in 1999. Intensified efforts currently are underway to reach the target as soon as possible after 2000 in the three remaining polio-endemic WHO regions (African Region, Eastern Mediterranean Region, and South-East Asia Region). Even in polio-endemic regions, many countries are already polio free as the geographic extent of poliovirus shrinks while others. especially those experiencing conflict and war, pose substantial challenges to implementing the proven polio eradication strategies. Increasing attention and research now are devoted to the certification of polio eradication in the polio-free regions (that will include the first phase of implementing the Global Plan of Action for the laboratory containment of wild poliovirus) and formulating a policy for stopping all polio vaccination once eradication, containment, and global certification have been achieved. This report outlines the progress toward polio eradication and highlights some of the remaining issues and challenges that must be addressed before polio becomes a disease that future generations know only by history.

Poliovirus vaccines. Progress toward global poliomyelitis eradication and changing routine immunization recommendations in the United States.

Poliomyelitis prevention in the United States has relied virtually exclusively on OPV during the past 30 years. Starting in 1997, a major change in the poliomyelitis vaccination policy occurred, facilitated by substantial progress toward worldwide poliomyelitis eradication. A sequential schedule of IPV followed by OPV became the preferred means to prevent poliomyelitis, although an all-OPV and an all-IPV schedule were considered acceptable alternatives. In 1999, two doses of IPV were recommended to start the primary series, followed by two doses of either poliovirus vaccine. As of January 2000, an all-IPV schedule is currently being implemented in the United States for routine childhood vaccination. Several unusual features are associated with the major public health policy change from an all-OPV to a sequential schedule, including (1) the process of involving a neutral party (i.e., the IOM); (2) the perceived concerns expressed before the change in policy with regard to provider and parent compliance, which could affect the hard-earned gains in raising immunization coverage rates; (3) the ethical issues surrounding the change (e.g., societal versus individual protection) and the influence that a single case of VAPP may have on national policy; (4) the relative lack of importance of cost-effectiveness data; and (5) the weight of progress in the global polio eradication initiative spurring the change in the United States and, increasingly, in other industrialized countries. The IOM assisted in the evaluation of the national poliomyelitis vaccination policy in 1977 and again in 1988. The 1988 review recommended that a sequential IPV-OPV schedule be considered at such time that a combination vaccine becomes available. Also, the IOM raised several important questions. Extensive research to address the questions raised by the IOM had been conducted so that, in 1996, more data were available for the decision-making process. The primary reasons for the change in vaccination policy were (1) the continued occurrence of VAPP in the absence of indigenously acquired wildtype poliovirus-associated paralytic disease, (2) the reduced risk for importation and spread of wild-type poliovirus caused by the progress of the global polio eradication initiative, (3) evidence from vaccine trials that combined IPV-OPV schedules are safe and immunogenic, and (4) maintenance of high levels of population immunity to poliovirus. The global effect of a national change in poliomyelitis vaccination policy was also considered in this policy-making process. Some members of the public health and medical communities raised objections that an increased reliance on IPV in the United States could lead other countries, especially developing countries, to inappropriately abandon OPV and increase reliance on IPV for routine vaccination. Experience from the global smallpox eradication campaign indicated that this scenario was unlikely. The United States ceased vaccinating against smallpox in 1971, 6 years before smallpox was eliminated from the world, without jeopardizing the global smallpox campaign. Subsequently, the effect on the global eradication initiative has been negligible. This article illustrates the potential discrepancy between expressed theoretic concerns about the number of injections and the actual practice once vaccination policy recommendations become the standard of care and that appropriate training and education can overcome these initial concerns. The authors found that compliance with the recommended use of IPV for the first and second doses as part of the sequential schedule was high, independent of socioeconomic status and ethnicity. The need for additional injections did not present a barrier to completion of the recommended childhood immunization schedule. (ABSTRACT TRUNCATED)

Possible global strategies for stopping polio vaccination and how they could be harmonized.

One of the challenges of the polio eradication initiative over the next few years will be the formulation of an optimal strategy for stopping poliovirus vaccination after global certification of polio eradication has been accomplished. This strategy must maximize the benefits and minimize the risks. A number of strategies are currently under consideration, including: (i) synchronized global discontinuation of use of oral poliovirus vaccine (OPV); (ii) regional or subregional coordinated OPV discontinuation; and (iii) moving from trivalent to bivalent or monovalent OPV. Other options include moving from OPV to global use of IPV for an interim period before cessation of IPV use (to eliminate circulation of vaccine-derived poliovirus, if necessary) or development of new OPV strains that are not transmissible. Each of these strategies is associated with specific advantages (financial benefits for OPV discontinuation) and disadvantages (cost of switch to IPV) and inherent uncertainties (risk of continued poliovirus circulation in certain populations or prolonged virus replication in immunodeficient persons). An ambitious research agenda addresses the remaining questions and issues. Nevertheless, several generalities are already clear. Unprecedented collaboration between countries, regions, and indeed the entire world will be required to implement a global OPV discontinuation strategy Regulatory approval will be needed for an interim bivalent OPV or for monovalent OPV in many countries. Manufacturers will need sufficient lead time to produce sufficient quantities of IPV Finally, the financial implications for any of these strategies need to be considered. Whatever strategy is followed it will be necessary to stockpile supplies of a poliovirus-containing vaccine (most probably all three types of monovalent OPV), and to develop contingency plans to respond should an outbreak of polio occur after stopping vaccination.

Effect of cyclosporin A on B cell maturation and differentiation.

The activation and differentiation of resting B cells into Ig secreting cells are regulated by T cells, macrophages and their secreted factors. The present study evaluated the effect of cyclosporin A (CsA) on this process. Peripheral blood lymphomonocytes (PBMC) drawn from healthy donors were stimulated with protein A (PA) or with lipopolysaccharides plus pokeweed (LPS+PWM) in either the presence or the absence of CsA. Phenotypic B cell changes and immunoglobulin production was then analyzed. The data revealed that CsA decreased the expression of B cell surface receptors of the activation phase, and enhanced the resting phase receptors. Different effects of CsA were found on B cell differentiation, depending on its induction by PA or LPS+PWM. In the first system, CsA decreased the expression of differentiation phase receptors and the secretion of free Ig. In cultures stimulated with LPS+PWM, CsA increased the differentiated phase receptors and Ig secretion. Thus, CsA seemed to act as a blocking agent of the activation phase and as a modulator of the differentiation phase and of IgG secretion, depending upon the antigen used for stimulation.

Induction and regulation of cytotoxic T cells by microbial antigens and recombinant interleukin 2.

The proliferation and development of cytotoxic T cells was investigated in human peripheral blood mononuclear cell (PBMC) cultures stimulated with an antigenic extract from Candida albicans (MPPS), or with the purified protein derivative from Mycobacterium tuberculosis (PPD), or with human recombinant interleukin 2 (rIL-2). Microbial antigen- and rIL-2-induced cytotoxic T cells were able to lyse both natural killer (NK) sensitive and resistant targets. No correlation was observed between the development of T cell cytotoxicity and interferon (IFN) production in vitro. The addition of anti-class II monoclonal antibodies at the beginning of MPPS/PPD-stimulated cultures inhibited the cell proliferation, IFN production and T cell cytotoxicity, while all these cellular activities were not inhibited by anti-class II antibodies in rIL-2-stimulated cultures. Finally, antibodies to class I determinants inhibit T cell cytotoxicity, suggesting a role of such determinants in the development of the non-adaptive immunity to microbial infections.

Plasma cell leukemia: a report on three patients.

Three patients with plasma cell leukemia are reported. Two of them has a previous history of myeloma; the third one started with a plasma cell leukemia. Diagnosis was made from the required presence of 20% plasma cells in the peripheral blood. In all 3 cases, bone marrow aspiration and peripheral blood showed plasma cells strongly positive for acid phosphatase and alpha-naphthyl acetate esterase, and negative for periodic acid-Schiff. The first patient was treated with a polychemotherapy regimen that included vincristine, cyclophosphamide, chlorambucil and prednisone, and the second patient with melphalan and prednisone; the third one, who started with plasma cell leukemia, received total body irradiation at the dose of 600 rad. The results of the therapy and survival time, which was never more than 3 months, are in accord with other reports in the literature.

Current epidemiology of pertussis in the United States.

The incidence of pertussis in the United States decreased rapidly during the 20th century, with the most impressive decreases resulting from the widespread use of DTP vaccine since the late 1940's. As a result of immunization laws, vaccine coverage levels against pertussis at school entry have been greater than 95% since 1980. National surveillance for pertussis done by the Centers for Disease Control (CDC) consists of two parts: a weekly telephone reporting system and a written case report system providing more detailed demographic, clinical, and laboratory information. In addition, data on secondary spread of pertussis among household contacts of reported cases were available on a small proportion of reported cases during 1979-1983. During the period 1980-1986, a total of 17,396 cases of pertussis was reported to CDC by weekly telephone reports. The annual incidence of reported pertussis rose during this period from 0.5 cases per 100,000 population to 1.7/100,000. Infants less than 12 months of age had the highest average annual incidence, estimated at 32 cases per 100,000. Children 1-4 years of age accounted for 25% of all cases but had an average annual incidence only 1/7th that of infants. The incidence rates for all age groups increased consistently between 1982 and 1986. The most impressive relative increases occurred among older adolescents and persons 20 years of age and older. In 1986, 10% of reported cases were in this age group compared to only 5% in 1982. Rates of hospitalization and complications such as pneumonia, seizures, and encephalopathy associated with pertussis were highest in children less than 6 months of age and declined progressively with increasing age.(ABSTRACT TRUNCATED AT 250 WORDS)

Inverse relationship between spontaneous interleukin-1 production and mitogen-driven proliferation in patients with pulmonary tuberculosis.

The blastogenic response to mitogens of peripheral blood mononuclear cells (PBMC) obtained from healthy volunteers and patients with chronic or acute tuberculosis (TB) was evaluated. Cells derived from TB patients showed a reduced proliferative capacity compared to that of healthy individuals. Three possible causes of such an impairment were investigated, namely: 1) a change in the proportion of lymphocyte subpopulations; 2) an altered ratio between monocytes and lymphocytes and 3) a reduction in the state of monocyte-macrophage activation, with an impaired production of interleukin-1 (IL-1). We observed no significant modification of lymphocyte subsets from TB patients and normal individuals. However, the relative number of monocytes in the patients was always higher than the controls. Furthermore, circulating monocytes from the patients with TB exhibited a decreased phagocytosis of latex beads, a normal expression of DR antigens, and an increased spontaneous production of IL-1. The possibility that the hyperactivation of macrophages may be responsible for the observed low blastogenic response is discussed.