Evaluation of meningococcal meningitis vaccination strategies for the meningitis belt in Africa.

BACKGROUND: Although the meningococcal polysaccharide vaccine has contributed to the control of Group A meningitis in the "meningitis belt" of Africa, recurrent large outbreaks have led to questions regarding vaccination strategy. We evaluated current and hypothetical vaccination strategies for the region. METHODS: A model was formulated to analyze the effectiveness and costs of vaccine campaigns in response to outbreaks based on 7 years of weekly incidence data from Burkina Faso. Additional models analyzed the potential impact and costs of either a 1- or 4-dose routine scheduled delivery of meningococcal polysaccharide vaccine based on data reported to the World Health Organization from 16 countries during 1948 through 1996. Vaccine efficacy, vaccination coverage and economic data from literature reviews provided model assumptions. RESULTS: For Burkina Faso neither 1- nor 4-dose vaccination schedules would prevent >30% of meningitis cases compared with the 42% prevented through an outbreak response program of vaccinating districts, which reach an incidence of 15 per 100000 persons for 2 weeks. For the entire meningitis belt, routine coverage with the 1- or 4-dose schedule meningococcal vaccine would require 4.9 and 19.6 million doses annually, respectively, for an annual net cost of $4.4 to $12.3 million and prevent an average 10300 to 12600 cases (23 to 28%), assuming a long term vaccine efficacy of 50%. In addition an initial "catch-up" campaign costing up to $72 million to vaccinate the population from 1 to 30 years of age would be required before achieving that level of effectiveness. CONCLUSION: Given the relatively poor routine vaccination coverage in this region, current strategies of vaccination campaigns that achieve higher coverage would generally be more effective and less costly than the modeled routine scheduled programs, assuming that campaigns can be rapidly implemented. Until a better vaccine is available, countries in this region would be more efficient in improving the response times to outbreaks, perhaps through improved surveillance, and in bolstering existing vaccination infrastructures rather than embarking on strategies of questionable effectiveness.

Opportunities for prevention of perinatal group B streptococcal disease: a multistate surveillance analysis. The Neonatal Group B Streptococcal Disease Study Group.

OBJECTIVE: To evaluate the potential impact of ACOG and Centers for Disease Control and Prevention (CDC) consensus strategies for the prevention of perinatal group B streptococcal disease. METHODS: We evaluated cases of early-onset group B streptococcal disease identified by active surveillance during 1995, in four areas in North America with an aggregate 186,000 births per year. We reviewed the hospital records of mothers and infants and any prenatal records available on site. Cases were determined to be preventable based on whether group B streptococcal screening could have been performed prenatally, sensitivity of screening, presence of obstetric complications, and opportunity to administer antibiotics. RESULTS: We reviewed records for 245 of 246 infants with early-onset group B streptococcal disease in the surveillance areas. Most of the 53 case-mothers who delivered preterm and 192 who delivered full-term had had at least one prenatal visit (83% and 99%, respectively). Few case-mothers had prenatal group B streptococcal screening cultures, although compliance was high for other prenatal screening tests. Fifty-four percent of case-mothers had a recognized obstetric risk factor for group B streptococcal disease: labor or rupture of membranes at less than 37 weeks, rupture of membranes for 18 hours on longer, or temperature 38C or greater. The estimated preventable portion of early-onset group B streptococcal cases was 78% for the screening-based approach (range 74% to 82% by area), compared with 41% for the risk-based approach (range 39% to 53% by area). CONCLUSION: Comprehensive implementation of either of the recommended prevention strategies could potentially prevent a substantial proportion of early-onset group B streptococcal disease.

Meningococcal vaccines.

Global control and prevention of meningococcal disease depends on the further development of vaccines that overcome the limitations of the current polysaccharide vaccines. Protein-polysaccharide conjugate vaccines likely will address the marginal protective antibody responses and short duration of immunity in young children derived from the A, C, Y, and W-135 capsular polysaccharides, but they will be expensive to produce and purchase, and may not offer a practical solution to the countries with greatest need. In addition, OMP vaccines have been tested extensively in humans and hold some promise in the development of a serogroup B vaccine, but are limited by the antigenic variability of these subcapsular antigens and the resulting strain-specific protection. Elimination of meningococcal disease likely will require a novel approach to vaccine development, ideally incorporating a safe and effective antigen or antigens common to all meningoccocal serogroups. As a solely human pathogen, however, N. meningitidis has developed many tools with which to evade the human immune system, and likely will pose a formidable challenge for years to come.

Global surveillance for meningococcal disease.

The word "surveillance" probably first referred to close supervision of individuals exposed to an infectious disease and their close contacts (1). Currently, though, surveillance refers more frequently to the ongoing accumulation of data so that it can be used for decision-making. A surveillance system includes collection, analysis, and dissemination of data. Surveillance can be used to evaluate trends in disease, to identify outbreaks, to test hypotheses, to evaluate existing programs, and to plan for new programs. Surveillance is the single most important tool for identifying infectious diseases that are emerging, are causing serious public health problems, or are diminishing in importance (2).

Epidemiology of meningococcal disease in north america.

Invasive disease caused by Neisseria meningitidis is one of the leading infectious causes of death in childhood in North America (1), but its prevention has not received the same priority on the health agenda as in Europe, Australia, and New Zealand. There are several likely explanations, but the principal one is that disease incidence appears to be lower in both Canada (2) and the United States (3) than in some of these other countries (4,5). Here, we describe recent epidemiological data concerning meningococcal infection in Canada and the United States and comment on the possible future introduction of vaccination to prevent meningococcal disease across the continent.

Update on Haemophilus influenzae serotype b and meningococcal vaccines.

Use of conjugate Haemophilus influenzae type b (Hib) vaccines has resulted in the near elimination of Hib invasive disease among infants in the United States in only 10 years, which places this intervention among the most notable public health achievements of the past decade. This has radically altered our perception of the major causes of bacterial meningitis and invasive bacterial disease among children, increasing the prominence of meningococcal disease as an important cause of childhood and adult meningitis and leading researchers to apply the same conjugate technology to the development of improved vaccines for Neisseria meningitidis. Use of conjugated meningococcal vaccines against serogroups A, C, Y, and W-135 are expected to offer the possibility of better control of sporadic disease and outbreaks throughout developed and developing countries within the next 5 years.

[Detection of meningococcal meningitis epidemics in Africa: a new recommendation]. / Mieux détecter les épidémies de méningite à méningocoque en Afrique: une nouvelle recommandation.

In sub-Saharan Africa, the control of meningococcal meningitis epidemics relies on early epidemic detection and mass vaccination. However, experience shows that interventions are often initiated too late to have a significant impact on the epidemic. A new recommendation drafted by participants of a consensus meeting proposes an alert threshold and an epidemic threshold based on the weekly number or incidence of meningitis cases, according to the population size and the epidemic risk, resulting in indicators with high sensitivity and specificity for the detection of an emerging epidemic. Meningitis outbreak investigations must include an assessment of the quality of epidemiologic surveillance. The new recommendation is published in English and French in the Weekly Epidemiologic Record [12]. The success of this consensus meeting shows the value of integrating results from surveillance, field experience and operational research for designing new health strategies.

Establishment of an active laboratory-based surveillance for bacterial meningitis in Croatia and molecular characterization of Neisseria meningitidis isolates causing meningococcal disease that were collected in the year 2000, the first year of activity.

In 2000, 23 Neisseria meningitidis (meningococcal [Men]) isolates were collected in Croatia through an active laboratory-based surveillance for bacterial meningitis (17 Men serogroup B [MenB], 4 MenC, 1 MenW135, and 1 nongroupable isolate). Molecular characterization revealed a substantial level of diversity with only six isolates belonging to electrophoretic type 5 (ET-5) and ET-37 hypervirulent complexes.

Cleavase fragment length polymorphism analysis of Neisseria meningitidis basic metabolic genes.

Cleavase fragment length polymorphism (CFLP) is a subtyping system based on the property of the enzyme cleavase to recognize junctions between single- and double-stranded regions of DNA formed after denaturation and cooling. To assess the capacity of CFLP for discriminating Neisseria meningitidis serogroup B strains belonging to the electrophoretic type (ET) 5 (ET-5) complex from other serogroup B strains, 30 serogroup B N. meningitidis isolates were subtyped by CFLP with internal fragments of five housekeeping genes, adk, aspC, carA, dhp, and glnA. Two genes (glnA and carA) which demonstrated a high degree of diversity for the serogroup B isolates were then used to further evaluate the suitability of CFLP for screening 50 serogroup C N. meningitidis outbreak-associated and sporadic-case isolates with a single metabolic gene. The results were compared to those from multilocus enzyme electrophoresis (MEE), the current standard subtyping method. CFLP was able to distinguish the ET-5 complex isolates from other serogroup B isolates as efficiently as MEE. Furthermore, CFLP analysis of a single gene was sufficient to identify and cluster the serogroup C isolates belonging to the ET-37 complex from other, unrelated serogroup C isolates but was not capable of differentiating between the isolates of the major individual ETs of this complex (ET-17 and ET-24) causing most serogroup C meningococcal disease outbreaks in the United States. CFLP based on a single gene with a high degree of diversity but not under selective pressure can be applied to the rapid screening of a large number of isolates related to the recognized epidemic complex ET-5 or ET-37. Additionally, CFLP can be used as an initial screening tool to survey the amount of diversity in genes that might be used to develop a DNA sequence-based subtyping system.

Surveillance for meningococcal disease and strategies for use of conjugate meningococcal vaccines in the United States.

BACKGROUND: Neisseria meningitidis is a leading cause of bacterial meningitis in US; new capsular type-specific conjugate vaccines offer an opportunity for improved control of meningococcal disease. We evaluated the relative burdens of invasive meningococcal disease in US and examined the projected impact of various meningococcal conjugate vaccination strategies on rates of meningococcal disease. METHODS: Meningococcal disease incidence rates were determined from active, population-based surveillance in selected US areas. Models were created to determine impact of vaccination of infants, toddlers, adolescents or college students with meningococcal conjugate vaccines, with assumptions for vaccine coverage, efficacy and duration of protection. Although we examined possible conjugate vaccine formulations including serogroups A, C, Y and W-135, the final vaccine impact analysis excluded serogroups A and W-135. Outcome measures were cumulative meningococcal disease incidence, and incidence 10 years after initiating vaccination among 0-22-year-olds. RESULTS: In models of serogroup C+Y meningococcal conjugate vaccination of infants, toddlers and adolescents, the cumulative incidence of meningococcal disease was reduced by 54, 48 and 25%, respectively; the toddler strategy had the greatest impact per dose. After 10 years of routine meningococcal conjugate vaccination, meningococcal disease could be reduced by 50% and deaths by 64%. CONCLUSIONS: Use of meningococcal conjugate vaccine could markedly reduce meningococcal disease incidence. Our data, along with vaccine formulation and vaccination program considerations, will be important in determining the optimal choice of vaccination strategy.

Haemophilus influenzae Type b disease among Amish children in Pennsylvania: reasons for persistent disease.

OBJECTIVE: To identify reservoirs of Haemophilus influenzae type b (Hib) pharyngeal carriage and assess barriers to vaccination among 2 Amish communities in Pennsylvania. METHODS: We investigated recent cases, performed community surveys for Hib vaccination coverage and pharyngeal carriage, and administered a questionnaire assessing vaccination knowledge and attitudes to 298 members of 2 Amish communities (A and B) in Pennsylvania and, as a comparison group, 136 non-Amish family members who participated in state immunization clinics. From December 1999 to February 2000, 8 cases of invasive Hib disease occurred among children who were 5 years of age or younger in Pennsylvania. Six of the case-patients were from Amish communities. None of the children had been vaccinated. RESULTS: Among children who were 5 years of age or younger, Hib vaccine coverage was low in the 2 Amish communities: A (9 [28%] of 32) and B (3 [7%] of 41) compared with the non-Amish group (19 [95%] of 20). Hib carriage prevalence was higher in both Amish communities than in the non-Amish group (A: 3%; B: 8%; non-Amish: 0%). More households in community B had 1 or more Hib carriers than in community A (8 [28%] of 29 vs 3 [9%] of 32). Among Amish parents who did not vaccinate their children, only 25% (13 of 51) identified either religious or philosophical objections as a factor; 51% (26 of 51) reported that vaccinating was not a priority compared with other activities of daily life. Seventy-three percent (36 of 49) would vaccinate their children if vaccination were offered locally. CONCLUSIONS: Undervaccinated communities in the United States still exist and allow circulation of Hib strains, resulting in disease among susceptible children. Identification of undervaccinated populations, such as the Amish, and targeted education and vaccination campaigns are essential to achieving elimination of Hib disease.

Emergency vaccination against epidemic meningitis in Ghana: implications for the control of meningococcal disease in West Africa.

BACKGROUND: Recurrent epidemics of meningococcal disease have been reported throughout the African meningitis belt since description of the disease in 1912. Meningooccal polysaccharide vaccines can effectively prevent disease but the optimum strategy for their use in this setting has been controversial. We used data from an outbreak of meningococcal disease in northern Ghana in 1997 to assess the potential effect of different vaccination strategies. METHODS: We identified all reported cases of meningococcal meningitis and estimated the number of cases and deaths that could have been prevented by vaccination through use of a simple mathematical model. We then assessed the potential effect of different vaccination strategies and the burden of these strategies on the public-health system. FINDINGS: In the three affected regions in northern Ghana there were 18703 cases and 1356 deaths reported between November, 1996, and May, 1997. Vaccination began in the third week of February and continued to April, reaching 72% of the at-risk population and preventing an estimated 23% of cases and 18% of deaths. A strategy of routine childhood and adult immunisation would have prevented 61% of cases had this same rate of vaccine coverage been achieved and maintained before the epidemic. If vaccination had started after the onset of the epidemic in January, as currently advocated by WHO guidelines, a similar proportion (61%) of cases could have been prevented. INTERPRETATION: Prevention of epidemics of meningococal disease in west Africa will be difficult until long-lasting conjugate vaccines capable of interrupting transmission of Neisseria meningitidis can be incorporated into routine infant-immunisation schedules. Until then, the strategy of surveillance and response advocated by WHO is as effective and more practical than a strategy of routine childhood and adult vaccination with currently available polysaccharide vaccines.

PIP: This study assessed the potential effects of different vaccination strategies using data from the 1997 meningococcal outbreak in northern Ghana. Since the description of the disease in 1912, recurrent epidemics of meningococcal disease have been reported throughout the African meningitis belt. The use of meningococcal polysaccharide vaccines has been proven to effectively prevent the disease, although the method of vaccine distribution was disputable. Using a simple mathematical model, meningococcal meningitis cases and deaths, which could have been forestalled by vaccination, were identified, and the effect of developed vaccination strategies on the public health system was analyzed. About 18,703 cases and 1356 deaths were reported in 3 regions of northern Ghana between November 1996 and May 1997. Vaccination was conducted between February and April, which covered 72% of the high-risk population and prevented approximately 23% of cases and 18% of deaths. Routine childhood and adult immunization would have prevented 61% of cases had this same rate of vaccine coverage been achieved and maintained before the epidemic. This study suggests that the prevention of the meningococcal disease epidemic in West Africa would be difficult unless long-lasting conjugate vaccines are incorporated into routine infant immunization schedules. For now, the surveillance and response strategies advocated by the WHO serve as an effective and practical intervention.

Risk factors for meningococcal disease in college students.

CONTEXT: Elevated rates of meningococcal disease were noted among 18- to 22-year-olds in the mid-1990s. However, national data on rates of meningococcal disease in US college students were not collected until 1998. OBJECTIVES: To determine rates of meningococcal disease in US college students and to identify risk factors for meningococcal disease in this population. DESIGN, SETTING, AND PATIENTS: Prospective surveillance study with nested case-control study of US college students with meningococcal infection from September 1, 1998, to August 31, 1999. Fifty state health departments and 231 college health centers participated. MAIN OUTCOME MEASURES: Incidence of and risk factors for meningococcal disease in US college students. RESULTS: Ninety-six cases of meningococcal disease were identified. The incidence rate for undergraduates was 0.7 per 100 000 persons vs 1.4 per 100 000 for the general population of 18- to 23-year-old nonstudents (P<.001). Freshmen living in dormitories had the highest incidence rate at 5.1 per 100 000. Of the 79 case-patients for whom information was available, 54 (68%) had illness due to vaccine-preventable meningococcal serogroups. On multivariable analysis of case-control study data, freshmen who lived in dormitories had an elevated risk of meningococcal disease (matched odds ratio, 3.6; 95% confidence interval, 1.6-8.5; P =.003) compared with other college students. CONCLUSIONS: Freshmen who live in dormitories have an independent, elevated risk of meningococcal disease compared with other college students. Use of the currently available quadrivalent polysaccharide vaccine among college students could substantially decrease their risk of meningococcal disease.

Marijuana use and social networks in a community outbreak of meningococcal disease.

BACKGROUND: We examined the role of social networks and marijuana smoking in a community outbreak of infections due to Neisseria meningitidis. METHODS: We interviewed all patients and their contacts. Isolates were tested by pulsed field electrophoresis and multilocus enzyme electrophoresis. RESULTS: Nine cases of meningococcal disease occurred in the outbreak; isolates from seven cases with positive cultures were identical. Multiple overlapping social networks were found for case-patients and their contacts. All case-patients were linked by the marijuana-related activities of their contacts. CONCLUSION: Investigation of social networks and marijuana exposure might help identify close contacts of patients with meningococcal disease and help prevent secondary infections.

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.

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.

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.

Invasive meningococcal disease in adolescents and young adults.

CONTEXT: Incidence of invasive meningococcal disease has increased recently in persons aged 15 through 24 years. OBJECTIVE: To characterize meningococcal infection in adolescents and young adults in Maryland during the 1990s. DESIGN AND SETTING: Population-based surveillance study for meningococcal disease from January 1, 1990, through December 31, 1999, in Maryland. PATIENTS: Maryland residents diagnosed as having invasive meningococcal disease. MAIN OUTCOME MEASURE: Invasive meningococcal infection. RESULTS: Of 295 total cases, 71 (24.1%) occurred among persons aged 15 through 24 years. Sixteen (22.5%) of these cases were fatal. The annual incidence rate increased from 0.9 to 2.1 cases per 100 000 among 15 through 24 year olds (P =.01). The proportion of all disease increased from 16.0% to 28.9% (P =.03). The incidence and proportion of cases subsequently decreased to 1.0 and 16.4% in 1998 through 1999, respectively. Infection in 15 through 24 year olds was more likely to be fatal than infection in those younger than age 15 years (22.5% vs 4.6%; P =.001). Infection in 15 through 24 year olds, compared with those aged 25 years or older, was more likely to be associated with male sex (66.2% vs 34.8%; P<.001) and serogroup C infection (46.9% vs 20.2%; P<.001), respectively. Infections were potentially preventable with the licensed meningococcal vaccine in 82.8% of 15 through 24 year olds, 68.1% of those younger than 15 years, and 76.8% of adults aged 25 years or older. CONCLUSIONS: Incidence of meningococcal infection in 15 through 24 year olds in Maryland increased and then declined during the 1990s. Infection in this age group was associated with an unusually high case-fatality ratio, and the vast majority of cases were potentially vaccine preventable.