Meningococcal carriage in the African meningitis belt

A meningococcal serogroup A polysaccharide/tetanus toxoid conjugate vaccine (PsA‐TT) (MenAfriVac^?) is being deployed in countries of the African meningitis belt. Experience with other polysaccharide/protein conjugate vaccines has shown that an important part of their success has been their ability to prevent the acquisition of pharyngeal carriage and hence to stop transmission and induce herd immunity. If PsA‐TT is to achieve the goal of preventing epidemics, it must be able to prevent the acquisition of pharyngeal carriage as well as invasive meningococcal disease and whether PsA‐TT can prevent pharyngeal carriage needs to be determined. To address this issue, a consortium (the African Meningococcal Carriage (MenAfriCar) consortium) was established in 2009 to investigate the pattern of meningococcal carriage in countries of the African meningitis belt prior to and after the introduction of PsA‐TT. This article describes how the consortium was established, its objectives and the standardised field and laboratory methods that were used to achieve these objectives. The experience of the MenAfriCar consortium will help in planning future studies on the epidemiology of meningococcal carriage in countries of the African meningitis belt and elsewhere.     

An outbreak of serotype 1 Streptococcus pneumoniae meningitis in northern Ghana with features that are characteristic of Neisseria meningitidis meningitis epidemics

BACKGROUND: The Kassena-Nankana District (KND) of northern Ghana lies in the African meningitis belt, where epidemics of bacterial meningitis have been reoccurring every 8-12 years. These epidemics are generally caused by Neisseria meningitidis, an organism that is considered to be uniquely capable of causing meningitis epidemics. METHODS: We recruited all patients with suspected meningitis in the KND between 1998 and 2003. Cerebrospinal fluid samples were collected and analyzed by standard microbiological techniques. Bacterial isolates were subjected to serotyping, multilocus sequence typing (MLST), and antibiotic-resistance testing. RESULTS: A continual increase in the incidence of pneumococcal meningitis was observed from 2000 to 2003. This outbreak exhibited strong seasonality, a broad host age range, and clonal dominance, all of which are characteristic of meningococcal meningitis epidemics in the African meningitis belt. The case-fatality rate for pneumococcal meningitis was 44.4%; the majority of pneumococcal isolates were antibiotic sensitive and expressed the serotype 1 capsule. MLST revealed that these isolates belonged to a clonal complex dominated by sequence type (ST) 217 and its 2 single-locus variants, ST303 and ST612. CONCLUSIONS: The S. pneumoniae ST217 clonal complex represents a hypervirulent lineage with a high propensity to cause meningitis, and our results suggest that this lineage might have the potential to cause an epidemic. Serotype 1 is not included in the currently licensed pediatric heptavalent pneumococcal vaccine. Mass vaccination with a less complex conjugate vaccine that targets hypervirulent serotypes should, therefore, be considered.     

Meningococcal disease: risk for international travellers and vaccine strategies

International travel and migration facilitate the rapid intercontinental spread of meningococcal disease. Serogroup A and, less so serogroup C, have been responsible for epidemics in the past (mainly in Africa). In recent years, W135 has emerged (first in Saudi Arabia, then in West Africa) as a serogroup that requires attention. Serogroups X and Y are infrequent, but associated with slowly rising trends. There are significant variations in the incidence of meningococcal disease and the distribution of serogroups responsible for meningococcal disease, both geographically and with time. Vaccine strategies need to address this variation, and broad coverage against all serogroups for which vaccines are currently available should be offered to travellers. Tetravalent polysaccharide meningococcal vaccines are limited by their poor immunogenicity in small infants and by the lack of long-term protection. In contrast, the novel tetravalent conjugate vaccine that is currently only available in North America is immunogenic in young infants, induces long-term protection and reduces nasopharyngeal carriage. The tetravalent conjugate meningococcal vaccine will be a leap forward in the control of meningococcal epidemics in affected countries. It will also boost the uptake of meningococcal vaccines in travellers because the duration of protection is longer and it eliminates the problem of immune hyporesponsiveness of serogroup C with repeated dosing. Current vaccine recommendations are to vaccinate all Hajj pilgrims, all travellers to areas with current outbreaks, travellers to the SubSaharan meningitis belt, and individuals with certain medical conditions.     

Meningococcal vaccine in travelers

PURPOSE OF REVIEW: New vaccines to prevent meningococcal disease have been licensed in recent years. It is therefore timely to discuss current vaccine strategies pertinent to international travelers in relation to the changing epidemiology. RECENT FINDINGS: Serogroup W135 achieved epidemic status in Africa in 2002, and then largely disappeared over a short time period. The year 2006 saw a marked epidemic rise in meningitis attack rates across the meningitis belt in Africa. This rise was mainly due to a new serogroup A strain, indicating that a new meningitis epidemic wave is beginning in Africa. Epidemics are also spreading south of the meningitis belt, including the Greater Lakes Area (Burundi, Rwanda, Republic of Tanzania). The new quadrivalent conjugate meningococcal vaccine is now licensed in North America but not elsewhere. In most other industrialized countries, the serogroup C conjugate vaccine is licensed. Plain polysaccharide quadrivalent vaccines are available almost worldwide. SUMMARY: Quadrivalent meningococcal vaccination is a visa requirement for Hajj and Umrah pilgrims to Saudi Arabia. Travelers to the meningitis belt during the dry season should be advised to receive meningococcal vaccine that covers all four serogroups. This recommendation should be extended to the Greater Lake Area, because of recent epidemics. Vaccine choices depend on availability.     

Advances with vaccination against Neisseria meningitidis

In the last decade, meningococcal serogroup C conjugate vaccination programs have been demonstrated to be hugely successful with a truly impressive public health impact. In sub‐Saharan Africa, with the implementation of an affordable serogroup A conjugate vaccine, it is hoped that a similar public health impact will be demonstrated. Challenges still remain in the quest to develop and implement broadly protective vaccines against serogroup B disease. New, broad coverage vaccines against serogroup B are for the first time becoming available although little is known about their antibody persistence, effectiveness or effect on nasopharyngeal carriage. Enhanced surveillance following any potential vaccine introduction against serogroup B needs to be thoroughly implemented. The future now holds a distinct possibility, globally, for substantially decreasing meningococcal disease, regardless of infecting serogroup.     

Meningococcal carriage in the African meningitis belt

In the African meningitis belt, epidemics of meningococcal disease occur periodically, although unpredictably, every few years. These epidemics continue to cause havoc but new efforts to control the disease, through the use of conjugate vaccines, are being made. Conjugate vaccines are likely to reduce meningococcal carriage, thus generating herd immunity, but to understand their potential impact we need to know more about the epidemiology of meningococcal carriage in Africa. We review published studies of meningococcal carriage in the African meningitis belt. A wide range of carriage prevalences has been reported, from 3% to over 30%, and the serogroup distribution has been variable. Factors influencing carriage include age, contact with a case, and the epidemic/endemic situation; however, season and immunisation with polysaccharide vaccine have little effect. Since the dynamics of carriage within a population are complex, longitudinal carriage studies are of great value; however, few such studies have been done. Carefully designed carriage studies are needed to measure and interpret the impact of meningococcal group A conjugate vaccines in Africa.     

Bacterial meningitis vaccines: Not just for kids

Bacterial meningitis remains a feared diagnosis that may lead to significant mortality and morbidity in both the developed and developing world; case fatality rates range from 10% to 50% among all age groups. Several vaccines are available (including the Haemophilus influenzae type B polysaccharide conjugate vaccine) that have proven effective in reducing the incidence of bacterial meningitis. Although a 23-valent pneumococcal polysaccharide vaccine has been available for some time, use of the 7-valent pneumococcal conjugate vaccine (PCV) has demonstrated a dramatic reduction in the incidence of invasive pneumococcal disease; despite the increase in the disease caused by nonvaccine-serotype strains, the success of the 7-valent PCV is noteworthy. A quadrivalent conjugate meningococcal vaccine has been available in the United States since 2005; although its true efficacy remains to be determined, there have been dramatic results with declining incidence in certain high-risk populations and in endemic areas.     

A critical review of control strategies against meningococcal meningitis epidemics in sub-Saharan African countries

The control strategy of meningitis epidemics in sub-Saharan countries, although reexamined regularly, is based on epidemiological, immunological and logistical considerations put forward at the end of the 1970s. It comprises organizing large-scale vaccinations in the event of a declared epidemic. The obvious failure of this strategy recommended by the World Health Organization (WHO) necessitates evaluation of the emergency vaccination criteria. Despite current controversy on the immunogenicity of the polysaccharide vaccine, its safety, effectiveness in the field and low cost could justify the reopening of a debate on its use in routine vaccination. Routine - or preventive - vaccination could significantly reduce the incidence of meningococcal meningitis and its severity. The conjugate vaccine, when available, will constitute an additional advantage in the prevention of meningococcal meningitis. A strategy combining both polysaccharide and conjugate vaccines according to the population targets and possibilities for funding remain to be defined. Received: January 16, 2002 · Revision accepted: April 23, 2002     

Meningococcal disease and control in China: Findings and updates from the Global Meningococcal Initiative (GMI)

The Global Meningococcal Initiative (GMI) is a global expert group, including scientists, clinicians and public health officials from a wide range of specialities. The goal of the GMI is to prevent meningococcal disease worldwide through education, research, and co-operation. The Chinese GMI roundtable meeting was held in June 2017. The GMI met with local experts to gain insight into the meningococcal disease burden in China and current prevention and vaccination strategies in place. China experienced five epidemics of serogroup A meningococcal disease (MenA) between 1938 and 1977, with peak incidence of 403/100,000 recorded in 1967. MenA incidence rates have significantly declined following the universal introduction of the MenA polysaccharide vaccine in China in the 1980s. Further, surveillance data indicates changing meningococcal epidemiology in China with the emergence of new clones of serogroup B from serogroup C clonal complex (cc) 4821 due to capsular switching, and the international spread of serogroup W cc11. The importance of carriage and herd protection for controlling meningococcal disease was highlighted with the view to introduce conjugate vaccines and serogroup B vaccines into the national immunization schedule. Improved disease surveillance and standardized laboratory techniques across and within provinces will ensure optimal epidemiological monitoring.     

Selective primary health care: strategies for control of disease in the developing world. XIII. Acute bacterial meningitis

Three species of bacteria (Haemophilus influenzae type b, Neisseria meningitidis, and Streptococcus pneumoniae) cause approximately three-quarters of all cases of acute bacterial meningitis in industrialized and developing countries. Infections due to N. meningitidis, S. pneumoniae, and H. influenzae type b are endemic in most countries; major epidemics of meningococcal disease still occur regularly, especially in sub- Saharan Africa. Such epidemics may be large, involving many thousands of patients, with a mortality that can exceed 10%. Both chemoprophylaxis and immunization are used to prevent meningococcal, pneumococcal, and H. influenzae type b meningitis. Chemoprophylaxis may involve the use of expensive antibiotics, and it can encourage the emergence of drug resistance. Mass immunization with meningococcal polysaccharide vaccine can effectively halt an epidemic of group A or group C meningococcal disease, and immunization protects close contacts. However, polysaccharide vaccines are ineffective in infants, who are very susceptible to bacterial meningitis. New protein-polysaccharide conjugated vaccines may be more effective in this young population.     

Prevention of bacterial meningitis. Vaccines and chemoprophylaxis

The morbidity and mortality caused by bacterial meningitis remains significant despite advances in antimicrobial therapy and supportive care. Prevention of meningitis by routine immunization of infants, who are at greatest risk, offers the only practical way of reducing the incidence of this disease. Widespread use of the recently developed protein conjugate vaccines against Haemophilus influenzae type b by itself could reduce the incidence of bacterial meningitis in the U.S. by more than half. To prevent disease caused by the other pathogens, an effective vaccine against the group B meningococcus must be developed, and the immunogenicity of the pneumococcal and quadrivalent meningococcal vaccines should be improved. Until such time that universal immunization of infants with highly immunogenic vaccines is possible, continued efforts must focus on targeting immunization at high-risk individuals and using chemoprophylaxis to prevent secondary disease where indicated. Addendum: On October 4, 1990, the U.S. Food and Drug Administration licensed the praxis Haemophilus influenzae type b-protein conjugate vaccine (Hboc) for use in infants at 2, 4, and 6 months of age with a booster dose at 15-18 months. Physicians are directed to statements by the Immunizations Practices Advisory Committee and the American Academy of Pediatrics for official recommendations concerning its use.     

The epidemiology of meningococcal disease in India

Objective To undertake a review of the literature on the epidemiology of meningococcal disease in India, with a view to informing future control policies. Methods We searched the PUBMED, EMBASE, Global Health, IMSEAR and MedIND databases for observational studies relating to the burden of endemic meningococcal disease in India, the occurrence and epidemiological characteristics of epidemics, and the prevalence of individual meningococcal serogroups. Results The relatively few reports identified suggest that the incidence of endemic meningococcal disease in India is low, but that occasional epidemics of meningococcal disease have been recorded for at least 100 years. The larger epidemics have affected mainly the cities of northern India and have almost universally been caused by meningococci belonging to serogroup A. These epidemics have showed a few characteristics, including a marked seasonality, which are similar to those of epidemic meningococcal A disease in Africa. Conclusions New serogroup A‐containing meningococcal conjugate vaccines are now being developed and reaching the market, including an affordable monovalent serogroup A vaccine manufactured in India, but intended primarily for use in Africa. These new tools may have a role in containing future Indian epidemics, but their usefulness is dependent on early identification of epidemics. This will require a functional disease surveillance system with adequate laboratory support throughout India.     

Hospital surveillance of childhood bacterial meningitis in Senegal and the introduction of Haemophilus influenzae type b conjugate vaccine

Bacterial meningitis is an important cause of morbidity and mortality in children living in low-resource settings. Pediatric bacterial meningitis cases < 5 years of age were identified through a regional hospital surveillance system for 3 years after introduction of routine immunization with Haemophilus influenzae type b (Hib) conjugate vaccine in Senegal in July 2005. Cases from the national pediatric hospital were also tracked from 2002 to 2008. The regional surveillance system recorded 1,711 suspected pediatric bacterial meningitis cases. Of 214 laboratory-confirmed cases, 108 (50%) were caused by Streptococcus pneumoniae, 42 (20%) to Hib, and 13 (6%) to Neisseria meningitidis. There was a 98% reduction in the number of hospitalized Hib meningitis cases from Dakar Region in 2008 compared with 2002. The surveillance system provides important information to the Ministry of Health as they consider self-funding Hib vaccine and introducing pneumococcal vaccine.     

Microbiological epidemiological history of meningococcal disease in Rio de Janeiro,Brazil

The main objectives of the present study were to investigate the clinical and laboratory features of meningococcal disease in the city of Rio de Janeiro, Brazil, during the overlap of 2 epidemics in the 1990s. We conducted a study of a series of cases of meningococcal disease admitted in a Meningitis Reference Hospital. All clinical isolates available were analyzed by means of microbiological epidemiological markers. In 1990, Neisseria meningitidis serogroup B:4,7:P1.19,15, 1.7,1 sulfadiazine-resistant of the ET-5 complex emerged causing epidemic disease. Despite mass vaccination campaign (VaMengoc B+C^®), the ET-5 clone remained hyperendemic after the epidemic peaked. In 1993 to 1995, an epidemic of serogroup C belonged to the cluster A4 overlapped, with a significant shift in the age distribution toward older age groups and an increase of sepsis. Serogroup C epidemics are a recurrent problem in Rio de Janeiro, which can be hindered with the introduction of a conjugate vaccine. We hope the data presented here brings useful information to discuss vaccines strategies and early management of suspected cases.     

Changes in serotype distribution may hamper efficacy of pneumococcal conjugate vaccines in children.

During the last 10 y we have observed an increased incidence of pneumococcal bacteremia in Sweden. In order to study the serotype distribution over time we collected 1136 invasive pneumococcal isolates from 1987, 1992 and 1997 from Swedish microbiological laboratories. Currently, new pneumococcal conjugate vaccines are being considered for introduction in the general childhood vaccination program in several countries, including Sweden. We studied the potential vaccine coverage rate for the new conjugate vaccines among our Swedish invasive isolates. We found that the serotype distribution fluctuated with time and observed a surprisingly low potential coverage rate for the 7-valent vaccine in Sweden, in contrast to other countries. Therefore we argue that pneumococcal conjugate vaccines have to be tailored to suit current, local serotype patterns and most likely will need to be changed over time.     

Preventive immunisation could reduce the risk of meningococcal epidemics in the African meningitis belt

Control of meningitis epidemics is based on early case detection followed by mass campaigns of immunisation. However, this strategy showed severe inadequacies during recent outbreaks in Africa. In Niamey, Niger, meningococcal vaccinations began in 1978 and detailed bacteriological and epidemiological surveillance of meningitis started in 1981. When vaccine coverage rates were higher than 50%, the prevalences of Neisseria meningitidis A meningitis were low in Niamey, although there was a concurrent epidemic in rural Niger. A massive outbreak of meningitis in Niamey in 1994-1995 followed a 6-year period during which the mean rate of vaccine coverage remained < 25%. The data indicate that, in the meningitis belt, preventive immunization should avoid a great number of deaths and be less expensive than mass immunisation campaigns performed after epidemics have begun.     

Definition and characterization of localised meningitis epidemics in Burkina Faso: a longitudinal retrospective study

Background  

The epidemiology of meningococcal meningitis in the African meningitis belt is characterised by seasonality, localised epidemics and epidemic waves. To facilitate research and surveillance, we aimed to develop a definition for localised epidemics to be used in real-time surveillance based on weekly case reports at the health centre level.     

Epidemic meningitis, meningococcaemia, and Neisseria meningitidis

Meningococcus, an obligate human bacterial pathogen, remains a worldwide and devastating cause of epidemic meningitis and sepsis. However, advances have been made in our understanding of meningococcal biology and pathogenesis, global epidemiology, transmission and carriage, host susceptibility, pathophysiology, and clinical presentations. Approaches to diagnosis, treatment, and chemoprophylaxis are now in use on the basis of these advances. Importantly, the next generation of meningococcal conjugate vaccines for serogroups A, C, Y, W-135, and broadly effective serogroup B vaccines are on the horizon, which could eliminate the organism as a major threat to human health in industrialised countries in the next decade. The crucial challenge will be effective introduction of new meningococcal vaccines into developing countries, especially in sub-Saharan Africa, where they are urgently needed.     

Prevention of Pneumococcal Meningitis

With the success of the conjugated Haemophilus influenzae type b vaccines, Streptococcus pneumoniae has become one of the most important causes of bacterial meningitis worldwide, causing significant morbidity and mortality. Additionally, the increasing amount of resistance that this organism is developing to multiple classes of antimicrobial agents has made the treatment of pneumococcal infections, especially meningitis, much more difficult. Immunization has been shown to be one of most effective methods for preventing pneumococcal meningitis, resulting not only in a decrease in disease burden, but also a decrease in antimicrobial resistance. Currently, a 23-valent pneumococcal polysaccharide vaccine and a heptavalent protein conjugate vaccine are licensed for use. However, the 23-valent polysaccharide vaccine is poorly immunogenic in infants and young children. The continued development, licensing, and use of pneumococcal conjugate vaccines have the best potential to both prevent disease and decrease the prevalence of pneumococcal meningitis.