Antimicrobial resistance of Neisseria meningitidis in the United States, 1997. The Active Bacterial Core Surveillance (ABCs) Team.
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Adolescent↗
Biomedical subjects
B A Perkins
Publications and source records attributed to B A Perkins.
Distribution of Neisseria meningitidis serogroup B serosubtypes and serotypes circulating in the United States. The Active Bacterial Core Surveillance Team.
Because the Neisseria meningitidis serogroup B (NMSB) capsule is poorly immunogenic in humans, immunization strategies have focused on noncapsular antigens. Both PorA and to a lesser extent PorB are noncapsular protein antigens capable of inducing protective bactericidal antibodies, and vaccines based on the outer membrane protein (OMP) components of serogroup B meningococci have been shown to be effective in clinical trials. Multiple PorA antigens seem to be needed to prevent endemic meningococcal disease around the world, and a hexavalent PorA-based meningococcal vaccine has recently been developed in The Netherlands. To evaluate the distribution of NMSB PorA and PorB antigens in the United States, serosubtyping and serotyping were done on 444 NMSB strains isolated in the active surveillance areas of the United States (total population, 32 million) during the period 1992 to 1998. A total of 244 strains were isolated from sporadic cases of meningococcal disease, and 200 strains were isolated from an epidemic in Oregon. A panel of 16 mouse monoclonal antibodies reactive with PorA and 15 monoclonal antibodies reactive with PorB were used. Among the NMSB isolates obtained from sporadic cases, the most prevalent serosubtypes were P1.7,16 (14.3%), P1.19,15 (9.8%), P1.7,1 (8.6%), P1.5,2 (7.8%), P1. 22a, 14 (7.8%), and P1.14 (5.3%) and the most prevalent serotypes were 4,7 (27.5%), 15 (16%), 14 (8.6%), 10 (6.1%), 1 (4.9%), and 2a (3.7%). A multivalent PorA-based OMP vaccine aimed at the six most prevalent serosubtypes could have targeted about half of the sporadic cases of NMSB disease that occurred between 1992 and 1998 in the surveillance areas. Twenty serosubtypes would have had to be included in a multivalent vaccine to achieve 80% coverage of strains causing sporadic disease. The relatively large number of isolates that did not react with murine monoclonal antibodies indicates that DNA sequence-based variable region typing of NMSB will be necessary to provide precise information on the distribution and diversity of PorA antigens and correlation with nonserosubtypeable isolates. The high degree of variability observed in the PorA and PorB proteins of NMSB in the United States suggests that vaccine strategies not based on OMPs should be further investigated.
Animals↗
Neisseria meningitidis serogroup B outer membrane vesicle vaccine in adults with occupational risk for meningococcal disease.
Vaccination provides a safe and effective means of reducing the risk of laboratory-acquired infection due to some Neisseria meningitidis serogroups. However, there is currently no serogroup B meningococcal vaccine licensed for use in the US. We used an investigational N. meningitidis serogroup B outer membrane vesicle (B:15:P1.7,16) vaccine produced by the National Institute of Public Health (NIPH) in Norway to immunize 20 researchers with occupational risk for disease. Three doses of vaccine were administered via intramuscular injection at 8-week intervals. The vaccine produced moderate or severe pain with 19 (33%) of the 58 doses administered. Reactions were similar following first, second and third doses. The number and severity of reactions peaked at 24 h postvaccination and then gradually waned. Of 16 vaccinees with results available from all blood draws, 12 (75%) showed a fourfold or greater rise in serum bactericidal activity (SBA) against the vaccine type-strain following two doses of vaccine, and 15 (94%) responded after three doses. Geometric mean titers increased by more than sixfold following two doses of vaccine when compared with prevaccination levels, and by more than 11-fold following a third dose. There was no significant difference between SBA measured using the vaccinee's own complement versus a donor complement source. The NIPH vaccine elicited an excellent bactericidal response against the vaccine type-strain in researchers with an occupational risk for disease. It may be useful for other laboratory personnel who routinely work with meningococcal strains containing similar outer membrane antigens. These findings reconfirm that the NIPH vaccine is immunogenic in adults and support the validity of using properly screened human donor complement in serum bactericidal assays against serogroup B meningococci.
Adult↗
Immunogenicity of 2 serogroup B outer-membrane protein meningococcal vaccines: a randomized controlled trial in Chile.
CONTEXT: Meningococcal disease occurs worldwide, and serogroup B disease accounts for a large proportion of cases. Although persons younger than 4 years are at greatest risk for serogroup B meningococcal disease, vaccine efficacy has not been demonstrated in this age group. OBJECTIVE: To evaluate serum bactericidal activity (SBA) against homologous vaccine type strains and a heterologous Chilean epidemic strain of Neisseria meningitidis as a potential correlate for vaccine efficacy. DESIGN: Double-blind, randomized controlled trial conducted between March 14 and July 20, 1994. All blood samples were taken by December 1994. SETTING: Santiago, Chile, where a clonal serogroup B meningococcal disease epidemic began in 1993. PARTICIPANTS: Infants younger than 1 year (n = 187), children aged 2 to 4 years (n = 183), and adults aged 17 to 30 years (n = 173). INTERVENTION: Participants received 3 doses of outer-membrane protein (OMP) meningococcal vaccine developed in either Cuba or Norway or a control vaccine, with each dose given 2 months apart. Blood samples were obtained at baseline, prior to dose 3, and at 4 to 6 weeks after dose 3. MAIN OUTCOME MEASURE: Immune response, defined as a 4-fold or greater rise in SBA titer 4 to 6 weeks after dose 3 compared with prevaccination titer. RESULTS: Children and adult recipients of either meningococcal vaccine were more likely than controls to develop an immune response to the heterologous epidemic strain. After 3 doses of vaccine, 31% to 35% of children responded to the vaccine vs 5% to placebo; 37% to 60% of adults responded to vaccine vs 4% to placebo (P<.05 vs control for all). Infants, however, did not respond. In contrast, against homologous vaccine type strains, the response rate was 67% or higher among children and adults and 90% or higher among infants (P<.001 vs control for all). Subsequent SBA against 7 isogenic homologous target strains identified class 1 OMP as the immunodominant antigen. CONCLUSIONS: These data suggest that neither serogroup B OMP meningococcal vaccine would confer protection during a heterologous epidemic. However, epidemic strain-specific vaccines homologous for class 1 OMP are promising candidates for the control of epidemic serogroup B meningococcal disease.
Adolescent↗
The epidemiology of candidemia in two United States cities: results of a population-based active surveillance.
We conducted prospective, active population-based surveillance for candidemia (defined as any Candida species isolated from blood) in Atlanta and San Francisco (total population, 5.34 million) during 1992-1993. The average annual incidence of candidemia at both sites was 8 per 100,000 population. The highest incidence (75 per 100,000) occurred among infants </=1 year old. In 19% of patients, candidemia developed prior to or on the day of admission. Underlying medical conditions included cancer (26%), abdominal surgery (14%), diabetes mellitus (13%), and human immunodeficiency virus infection (10%). In 47% of cases, species of Candida other than Candida albicans were isolated, most commonly Candida parapsilosis, Candida glabrata, and Candida tropicalis. Antifungal susceptibility testing of 394 isolates revealed minimal levels of azole resistance among C. albicans, C. tropicalis, and C. parapsilosis. These data document the substantial burden of candidemia and its changing epidemiology. Continued surveillance will be important to monitor the epidemiology of candidemia and to detect emergence of resistance to azoles.
Acquired Immunodeficiency Syndrome↗
Reemergence of invasive Haemophilus influenzae type b disease in a well-vaccinated population in remote Alaska.
Before vaccination, Alaska Natives experienced very high rates of invasive Haemophilus influenzae type b (Hib) disease and carriage. Vaccination with Hib conjugate vaccine PRP-OMP (polyribosylribitol phosphate Neisseria meningitidis outer membrane protein) began in 1991 and resulted in a sharp decline in cases. In 1996, after switching to a different Hib conjugate vaccine, DTP-HbOC (which combines diphtheria-tetanus-whole cell pertussis vaccines with HbOC [Hib oligosaccharide CRM197]), cases of invasive Hib disease increased, suggesting ongoing Hib transmission despite widespread vaccination. To determine the prevalence of and risk factors for carriage, a cross-sectional study of oropharyngeal Hib carriage was conducted among Alaska Native children aged 1-5 years in remote southwestern Alaska. Of 496 children with swabs taken, 46 (9.3%) were colonized with Hib. Carriage rates varied by village from 2.2% to 13.2% and by age from 6.1% in 1-year-olds to 14.7% in 5-year-olds. Crowding was associated with Hib carriage. Widespread vaccination with PRP-OMP Hib conjugate vaccine did not eliminate carriage in this population of Alaska Natives, and ongoing carriage contributed to disease resurgence.
Age Factors↗
The changing epidemiology of meningococcal disease in the United States, 1992-1996.
New meningococcal vaccines are undergoing clinical trials, and changes in the epidemiologic features of meningococcal disease will affect their use. Active laboratory-based, population-based US surveillance for meningococcal disease during 1992-1996 was used to project that 2400 cases of meningococcal disease occurred annually. Incidence was highest in infants; however, 32% of cases occurred in persons >/=30 years of age. Serogroup C caused 35% of cases; serogroup B, 32%; and serogroup Y, 26%. Increasing age (relative risk [RR], 1.01 per year), having an isolate obtained from blood (RR, 4.5), and serogroup C (RR, 1.6) were associated with increased case fatality. Among serogroup B isolates, the most commonly expressed serosubtype was P1.15; 68% of isolates expressed 1 of the 6 most common serosubtypes. Compared with cases occurring in previous years, recent cases are more likely to be caused by serogroup Y and to occur among older age groups. Ongoing surveillance is necessary to determine the stability of serogroup and serosubtype distribution.
Adolescent↗
Maternal cigarette smoking and invasive meningococcal disease: a cohort study among young children in metropolitan Atlanta, 1989-1996.
OBJECTIVES: This study assessed the association between maternal cigarette smoking during pregnancy and the risk of invasive meningococcal disease during early childhood. METHODS: Using a retrospective cohort study design, cases from an active surveillance project monitoring all invasive meningococcal disease in the metropolitan Atlanta area from 1989 to 1995 were merged with linked birth and death certificate data files. Children who had not died or acquired meningococcal disease were assumed to be alive and free of the illness. The Cox proportional hazards analysis was used to assess the independent association between maternal smoking and meningococcal disease. RESULTS: The crude rate of meningococcal disease was 5 times higher for children whose mothers smoked during pregnancy than for children whose mothers did not smoke (0.05% vs 0.01%). Multivariate analysis revealed that maternal smoking (risk ratio [RR] = 2.9; 95% confidence interval [CI] = 1.5, 5.7) and a mother's having fewer than 12 years of education (RR = 2.1; 95% CI = 1.0, 4.2) were independently associated with invasive meningococcal disease. CONCLUSIONS: Maternal smoking, a likely surrogate for tobacco smoke exposure following delivery, appears to be a modifiable risk factor for sporadic meningococcal disease in young children.
Adult↗
Efficacy of meningococcal vaccine and barriers to vaccination.
CONTEXT: Use of the quadrivalent meningococcal vaccine for control of outbreaks has increased in recent years, but the efficacy of meningococcal vaccine during mass vaccination campaigns in US civilian populations has not been assessed. OBJECTIVES: To evaluate the efficacy of the quadrivalent meningococcal vaccine against serogroup C meningococcal disease in a community outbreak setting and to evaluate potentially modifiable barriers to vaccination in an area with persistent meningococcal disease following immunization. DESIGN: Matched case-control study of vaccine efficacy using cases of serogroup C meningococcal disease in persons eligible for vaccination during mass vaccination campaigns. Control patients were matched by neighborhood and age. The control group was used to identify possible barriers to vaccination. SETTING: Gregg County, Texas, population 106076, from 1993 to 1995. PARTICIPANTS: A total of 17 case patients with serogroup C meningococcal disease eligible for vaccine and 84 control patients. MAIN OUTCOME MEASURES: Vaccine efficacy and risk factors associated with nonvaccination. RESULTS: Vaccine efficacy among 2- to 29-year-olds was 85% (95% confidence interval, 27%-97%) and did not change in bivariate analyses with other risk factors that were significant in univariate analysis. Among control patients, older age was strongly associated with nonvaccination; vaccination rates for 2- to 4-year-olds, 5- to 18-year-olds, and 19- to 29-year-olds were 67%, 48%, and 20%, respectively (chi2 for linear trend, P=.01). CONCLUSIONS: The meningococcal polysaccharide vaccine was effective against serogroup C meningococcal disease in this community outbreak. Although specific barriers to vaccination were not identified, older age was a risk factor for nonvaccination in the target population of 2- to 29-year-olds. In future outbreaks, emphasis should be placed on achieving high vaccination coverage, with special efforts to vaccinate young adults.
Adolescent↗
Epidemic leptospirosis associated with pulmonary hemorrhage-Nicaragua, 1995.
In October 1995, epidemic "hemorrhagic fever," without jaundice or renal manifestations, was reported in rural Nicaragua following heavy flooding; 2259 residents were evaluated for nonmalarial febrile illnesses (cumulative incidence, 6.1%) and 15 (0.7%) died with pulmonary hemorrhage. A case-control study found that case-patients were more likely than controls to have ever walked in creeks (matched odds ratio [MOR], 15.0; 95% confidence interval [CI], 1.7-132.3), have household rodents (MOR, 10.4; 95% CI, 1.1-97.1), or own dogs with titers >/=400 to Leptospira species (MOR, 23.4; 95% CI, 3.6-infinity). Twenty-six of 51 case-patients had serologic or postmortem evidence of acute leptospirosis. Leptospira species were isolated from case-patients and potential animal reservoirs. This leptospirosis epidemic likely resulted from exposure to flood waters contaminated by urine from infected animals, particularly dogs. Leptospirosis should be included in the differential diagnosis for nonmalarial febrile illness, particularly during periods of flooding or when pulmonary hemorrhage occurs.
Adolescent↗
Immunogenicity of two efficacious outer membrane protein-based serogroup B meningococcal vaccines among young adults in Iceland.
Serum bactericidal activity (SBA) and ELISA antibody levels elicited by two efficacious serogroup B meningococcal vaccines were measured in a controlled trial involving 408 15- to 20-year-olds. Subjects were given two doses at a 6-week interval of a serogroup B or control vaccine. Response was defined as > or = 4-fold rise in antibody level. After two doses of the Finlay Institute (Havana) vaccine at 12 months, the proportions of SBA and ELISA responders were not different from those of the control group (15% and 17% [vaccine] vs. 13% and 9% [control], P > .05). After two doses of the National Institute of Public Health (Oslo) vaccine, there were more SBA and ELISA responders than in the control group (47% and 34% [vaccine] vs. 10% and 1% [control]) or the Finlay Institute vaccine group (P < .05 for both). SBA and ELISA may be insensitive correlates for protective efficacy for some outer membrane protein-based serogroup B meningococcal vaccines.
Adolescent↗
Suspected Brazilian purpuric fever in a toddler with overwhelming Epstein-Barr virus infection.
We describe a toddler from Connecticut who developed purulent conjunctivitis, fever, and a morbilliform rash. Blood cultures were positive for Haemophilus influenzae biogroup aegyptius; further investigation was performed to assess the possibility that the illness was consistent with Brazilian purpuric fever, which, to our knowledge, has not been reported in the United States. This isolate shared morphological and some biochemical characteristics with previously studied H. influenzae biogroup aegyptius strains but differed according to slide agglutination testing, plasmid characterization, and ribotyping. Blood and tissue samples obtained during his hospitalization were also positive for Epstein-Barr virus. The child died 8 days after hospitalization. Fifty other cases of invasive H. influenzae infection were identified by active surveillance studies. Of the 49 viable surveillance isolates, 10 were biotype III (two of which had the same ribotype as the strain from our case.
Bacteremia↗
Meningococcal vaccine in sub-Saharan Africa.
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Adult↗
Bacterial meningitis in the United States in 1995. Active Surveillance Team.
BACKGROUND: Before the introduction of the conjugate vaccines, Haemophilus influenzae type b was the major cause of bacterial meningitis in the United States, and meningitis was primarily a disease of infants and young children. We describe the epidemiologic features of bacterial meningitis five years after the H. influenzae type b conjugate vaccines were licensed for routine immunization of infants. METHODS: Data were collected from active, population-based surveillance for culture-confirmed meningitis and other invasive bacterial disease during 1995 in laboratories serving all the acute care hospitals in 22 counties of four states (total population, more than 10 million). The rates were compared with those for 1986 obtained by similar surveillance. RESULTS: On the basis of 248 cases of bacterial meningitis in the surveillance areas, the rates of meningitis (per 100,000) for the major pathogens in 1995 were Streptococcus pneumoniae, 1.1; Neisseria meningitidis, 0.6; group B streptococcus, 0.3; Listeria monocytogenes, 0.2; and H. influenzae, 0.2. Group B streptococcus was the predominant pathogen among newborns, N. meningitidis among children 2 to 18 years old, and S. pneumoniae among adults. Pneumococcal meningitis had the highest case fatality rate (21 percent) and in 36 percent of cases was caused by organisms that were not susceptible to penicillin. From these data, we estimate that 5755 cases of bacterial meningitis were caused by these five pathogens in the United States in 1995, as compared with 12,920 cases in 1986, a reduction of 55 percent. The median age of persons with bacterial meningitis increased greatly, from 15 months in 1986 to 25 years in 1995, largely as a result of a 94 percent reduction in the number of cases of H. influenzae meningitis. CONCLUSIONS: Because of the vaccine-related decline in meningitis due to H. influenzae type b, bacterial meningitis in the United States is now a disease predominantly of adults rather than of infants and young children.
Adolescent↗
Tobacco smoke as a risk factor for meningococcal disease.
BACKGROUND: Since 1992 the US Pacific Northwest has experienced a substantial increase in the incidence of serogroup B meningococcal disease. The current meningococcal polysaccharide vaccine is poorly immunogenic in young children and does not protect against N. meningitidis serogroup B. Defining alternative approaches to the prevention and control of meningococcal disease is of considerable public health importance. METHODS: We performed a case-control study comparing 129 patients in Oregon and southwest Washington with 274 age- and area-matched controls. We used conditional logistic regression analysis to determine which exposures remained associated with disease after adjusting for other risk factors and confounders and calculated the proportion of disease attributable to modifiable exposures. RESULTS: After adjustment for all other significant exposures identified, having a mother who smokes was the strongest independent risk factor for invasive meningococcal disease in children < 18 years of age [odds ratio (OR), 3.8; 95% confidence interval (CI) 1.6 to 8.9)], with 37% (CI 15 to 65) of all cases in this age group potentially attributable to maternal smoking. Adult patients were more likely than controls to have a chronic underlying illness (OR 10.8, CI 2.7 to 43.3), passive tobacco smoke exposure (OR 2.5, CI 0.9 to 6.9) and to smoke tobacco (OR 2.4, CI 0.9 to 6.6). Dose-response effects were seen for passive smoke exposure and risk of disease in all age groups. CONCLUSION: Tobacco smoke exposure independently increases the risk of developing meningococcal disease.
Adolescent↗
Evaluation of an algorithm for integrated management of childhood illness in an area of Kenya with high malaria transmission.
In 1993, the World Health Organization completed the development of a draft algorithm for the integrated management of childhood illness (IMCI), which deals with acute respiratory infections, diarrhoea, malaria, measles, ear infections, malnutrition, and immunization status. The present study compares the performance of a minimally trained health worker to make a correct diagnosis using the draft IMCI algorithm with that of a fully trained paediatrician who had laboratory and radiological support. During the 14-month study period, 1795 children aged between 2 months and 5 years were enrolled from the outpatient paediatric clinic of Siaya District Hospital in western Kenya; 48% were female and the median age was 13 months. Fever, cough and diarrhoea were the most common chief complaints presented by 907 (51%), 395 (22%), and 199 (11%) of the children, respectively; 86% of the chief complaints were directly addressed by the IMCI algorithm. A total of 1210 children (67%) had Plasmodium falciparum infection and 1432 (80%) met the WHO definition for anaemia (haemoglobin < 11 g/dl). The sensitivities and specificities for classification of illness by the health worker using the IMCI algorithm compared to diagnosis by the physician were: pneumonia (97% sensitivity, 49% specificity); dehydration in children with diarrhoea (51%, 98%); malaria (100%, 0%); ear problem (98%, 2%); nutritional status (96%, 66%); and need for referral (42%, 94%). Detection of fever by laying a hand on the forehead was both sensitive and specific (91%, 77%). There was substantial clinical overlap between pneumonia and malaria (n = 895), and between malaria and malnutrition (n = 811). Based on the initial analysis of these data, some changes were made in the IMCI algorithm. This study provides important technical validation of the IMCI algorithm, but the performance of health workers should be monitored during the early part of their IMCI training.
Algorithms↗
Assessment of potential indicators for protein-energy malnutrition in the algorithm for integrated management of childhood illness.
Potential indicators were assessed for the two classifications of protein-energy malnutrition in the guidelines for integrated management of childhood illness: severe malnutrition, which requires immediate referral to hospital, and very low weight, which calls for feeding assessment, nutritional counselling and follow-up. Children aged < 2 years require feeding assessment and counselling as a preventive intervention. For severe malnutrition, we examined 1202 children admitted to a Kenyan hospital for any association of the indicators with mortality within one month. Bipedal oedema indicating kwashiorkor, and two marasmus indicators (visible severe wasting and weight-for-height (WFH) Z-score of < -3) were associated with a significantly increased mortality risk (odds ratios, 3.1-3.9). Very low weight-for-age (WFA) (Z-score of < -4.4) was not associated with an increased risk of mortality. Because first-level health facilities generally lack length-boards, bipedal oedema and visible severe wasting were chosen as indicators of severe malnutrition. To assess potential WFA thresholds for the very low weight classification, our primary source of data came from 1785 Kenyan outpatient children, but we also examined data from surveys in Nepal, Bolivia, and Togo. We examined the performance of WFA at various thresholds to identify children with low WFH and, for children aged < or = 2 years, low height-for-age (HFA). Use of a WFA threshold Z-score of < -2 identified a considerable proportion of children (from 13% in Bolivia to 68% in Nepal) which, in most settings, would pose an enormous burden on the health facility. Among ill children in Kenya, a threshold WFA Z-score of < -3 had a sensitivity of 89-100% to detect children with WFH Z-scores of < -3, and, with an identification rate of 9%, would avoid overburdening the clinics. Potential modifications include use of a more restrictive cut-off in countries with high rates of stunting, or the elimination of the WFA screen in order to concentrate efforts on intervention for all children below the 2-year age cut-off. Key issues in every country include the capacity to provide counselling for many children and linkage to nutritional improvement programmes in the community.
Age Factors↗