Epidemics of meningococcal meningitis in Northern Nigeria focus on preventive measures.

Throughout the past 200 years, epidemics of meningococcal infection have been noted in Northern Nigeria. Consequently, control of meningococcal meningitis is one of the major priorities in infection control in the region. The proportions of cases of invasive meningococcal disease (IMD) caused by the five common serotypes (A, B, C, Y, and W135) vary among different regions and within specific geographic locations. Hence, effective and comprehensive disease control can only be achieved with the use of vaccines that target all of these disease-causing serotypes. Vaccines for the majority of meningococcal serogroups implicated in causing IMD are available in developed countries and have proven effective in reducing the disease incidence. However, the overall success of a vaccine depends on its coverage of the at-risk population as well as safety and effectiveness of the vaccine at preventing disease. Therefore, maximizing the global impact of these vaccines requires having them made available in regions with the high incidence of the disease, like Northern Nigeria, where rates of meningococcal disease are several times higher than in industrialized nations, and the reported mortality is usually high.

INTRODUCTION

Meningococcal meningitis is an endemic disease with cosmopolitan mode of distribution and seasonal variations. The incidence can be as high as 1000/100,000 in some parts of the world, especially areas located within “meningitis belt” (a region of 25 Sub-Saharan countries stretching from Senegal in the west to Ethiopia in the east, with a total population of about (500 million people).[12] The epidemics usually start during the dry season and terminate when the rains start. Although the circumstances surrounding the recurrent episodes of meningitis are not well elucidated, environmental factors, such as humidity, dust concentrations, and a higher number of respiratory tract infections due to the cold nights, have been mentioned as possible factors.[3] Other risk factors for meningococcal disease include young age, dry season, overcrowding, active or passive smoking, and coinfections of respiratory pathogens.[4] The first episode of invasive meningococcal disease (IMD) was in Geneva in 1805,[5] while the first outbreak in Africa was reported in 1840,[6] and in 1905, the first major epidemic in West Africa was reported.[7] The most severe epidemic of meningococcal meningitis experienced by Africa was in 1996, with >150,000 reported cases and 16,000 deaths.

IMD is an acute, rapidly progressive, and unpredictable clinical condition that is associated with significant mortality and morbidity among those who are affected. Incidence of IMD is high among young adults (16–21 years old),[89] with case fatality ratio that ranges from approximately 10%–20%.[910111213] Furthermore, about 20% of IMD survivors experience significant complications, including amputation, deafness, chronic pain, skin ulceration, and neurologic deficits.[9] Central nervous system manifestations of meningococcal meningitis occur as a consequence of multifactorial pathological processes that include but are not limited to: (1) indirect inflammatory processes, such as cytokine release, ischemia, vasculitis, and edema, (2) direct bacterial toxicity, and (3) systemic effects, including shock, seizures, and cerebral hypoperfusion.

In addition, cerebral edema may be caused by increased secretion of cerebrospinal fluid (CSF), decreased reabsorption of CSF, and derangement in the function of blood–brain barrier. Increased intracranial pressure secondary to cerebral edema, loss of cerebrovascular autoregulation, and reduced arterial perfusion pressure secondary to shock reduce cerebral blood flow in bacterial meningitis,[14] with its attendant negative consequences on morbidity and mortality. Therefore, precautions should be taken to avoid transfer of the meningococcal bacteria from the infected person to others (which is primarily by coughing and sneezing). These precautions include covering the mouth and nose when sneezing or coughing, effective hand washing and drying after toileting and before eating or preparing food, and not sharing common utensils. In countries with high rate of transmission of meningococcal disease during epidemic, there is a need to vaccinate the at-risk population.

For instance, during the epidemics of meningitis in 2015, about 222,000 people were vaccinated in the early phase of the outbreak, which likely changed its course. However, due to the magnitude and rapid spread of the outbreak, reactive vaccination was not available for all affected areas, nor were there enough vaccines to reach herd immunity in some locations. As such, during future meningitis epidemic seasons, it will be important that these areas are monitored closely, along with other locations that did not receive vaccination.[15]

Introduction of conjugated vaccines against Neisseria meningitidis serogroup C has changed the epidemiology of community-acquired bacterial meningitis worldwide.[14] Epidemiologically, this outbreak emphasizes the potential for serotype shifts following introduction of Men A conjugate vaccine (MenAfrivac), which protects against the most prevalent type of N. Meningitidis (serogroup A).[1415]

The high rate of morbidity and mortality associated with meningococcemia has necessitated close monitoring of the disease in developed countries and an increased focus on vaccination as a means of prevention.[8] For example, in the United Kingdom, introduction of the serogroup C meningococcal vaccine for all children in 1999 led to significant decrease in serogroup C meningococcal disease by about 80%,[2] providing evidence that vaccine intervention might eventually halt spread of transmission. Hence, mass vaccination of high-risk populations, particularly during epidemics, is likely to be the most effective strategy for controlling meningococcal disease.[910] This review focuses on three major modalities of prevention: (1) immunoprophylaxis, (2) chemoprophylaxis, and (3) public enlightenment.

Immunoprophylaxis

Implementation of immunization recommendations in developed societies was accompanied by a substantial decrease in the incidence and prevalence of N. meningitidis infection, especially among adolescents.[1617] Furthermore, it was observed that conjugate vaccine protects not only vaccinated individuals but also the larger community (herd immunity), presumably as a result of reduced nasopharyngeal carriage of the organism among nasopharyngeal carriers.[91014]

To circumvent the dreadful effect of IMD, many developed societies have incorporated meningococcal vaccine in their routine immunization programs.[181920] However, meningococcal vaccines against serotype C are in limited supply, particularly in resource-limited countries in the “African meningitis belt.” Therefore, there is a need to provide cost-effective recommendations about the use of meningococcal vaccines and to suggest country-specific traditional methods of preventive measure against IMD.[21] There is also need to finance research and local production of vaccines in the region

Use of meningococcal C vaccine in Nigeria

Regional epidemiologic considerations have guided the development and use of meningococcal vaccines, which have been effective in the serogroup-specific reduction of IMD in areas where those vaccines have been used. One of the serious issues related to immunoprophylaxis is that most vaccines currently being used for meningitis C outbreaks in Nigeria are polysaccharide vaccines,[15] which are in short supply as they are being phased out in other parts of the world. In addition, more effective and long-lasting conjugate vaccines are not readily accessible for outbreak response in the country. This constitutes a strong limitation to control of outbreaks of serogroup C meningitis and calls for accelerated development of affordable and effective conjugate vaccines to cover all epidemic types.

Furthermore, effectiveness of serogroup C plain polysaccharide vaccines appears to be limited among infants and young children,[212223] probably due to its poor immunogenicity among children. In addition, these vaccines do not appear to induce immunologic memory, and repeated administration of plain polysaccharide vaccine leads to a state of immunologic hyporesponsiveness,[2242526] likely because of the T-cell-independent nature of immune responses to polysaccharide antigens. Therefore, plain polysaccharide vaccines might not be the appropriate vaccine candidates for preventing outbreaks of meningococcal disease particularly among children.

This informed the need for conjugate vaccines which may increase the effectiveness of polysaccharide capsule-based vaccines. Unlike plain polysaccharide vaccines, conjugate polysaccharide vaccines facilitate T-cell helper for specific antibody response and for induction of immunologic memory. Hence, antibody responses can be generated, even among infants.[2627282930]

In view of the above, it was postulated that mass immunization with polysaccharide conjugate vaccines might be an improved method and reliable strategy for the prevention of meningococcal disease during epidemics. This informed the recommendation for development of meningococcal serogroup C conjugate vaccine to control the increasing incidence and high mortality rate associated with an epidemic of serogroup C meningococcal disease in the United Kingdom in the 1990s.[163031]

Immunization schedule for targeted at-risk populations

Although the use of effective vaccines in industrialized countries has contributed significantly to bringing down the case fatality rate of IMD, protection was short lived, requiring a booster dose to protect through early adulthood and beyond.[914] In general, meningococcal vaccines are not long lasting, and they provide protection for 3–5 years only. Therefore, someone who has been previously vaccinated may no longer still be protected against the disease 5 years after the vaccination. This calls for an acceptable well-structured immunization schedule for targeted at-risk populations.

Vaccine is targeted at the following groups

Children under-five years of age are the most at risk from meningococcal C disease. Therefore, Men C vaccine is currently given to the following:

Children at 3 and 12 to 13 months of age and young children

Household members, roommates in dormitories, those who come into close contact with an infected person, and all unvaccinated family members

College students in their 1st year living in dormitories, military recruits and travelers to certain parts of the world, and children aged 2–23 months with complement deficiencies.

Vaccine schedule

Vaccines schedule for MenACWY-CRM is at ages 2, 4, 6, and 12 months, with booster doses 3 years after the initial vaccination series and every 5 years thereafter. In a related development, the Advisory Committee on Immunization Practices suggested that immunization with MenACWY should be given to persons within ages 11–18 years. The first dose is to be administered at 11–12 years of age, followed by a booster at age 16 years. A single dose may be given up until 21 years of age as a catch-up vaccination if a first dose has not been administered before the age of 16 years.[9] MenACWY also is recommended routinely for all individuals aged 9 months through 55 years who are considered to be at high risk for IMD.[9]

Chemoprophylaxis

Another effective strategy of preventing person-to-person transmission of N. meningitidis, especially among persons in close contact with patients who have meningococcal disease, is chemoprophylaxis.[323334] Antimicrobial chemoprophylaxis plays a significant role in preventing secondary cases of meningococcal disease, particularly in sporadic meningitis. Household members and other contacts of an infected person may be given antibiotic medications to prevent them from becoming infected. Person-to-person spread can be halted by administration of an antimicrobial that is effective in clearing the asymptomatic nasopharyngeal carrier state. Chemoprophylaxis is more effective when commenced within 24 h. Delay by >2 weeks may limit the effectiveness of chemoprophylaxis although it is still recommended up to a month after the onset of the disease.[35]

Prophylactic drugs

(1) Rifampicin – Rifampicin is recommended as a 2-day course. This should be followed by close observation and monitoring of close contacts for signs of disease. (2) Ciprofloxacin – A single dose of ciprofloxacin has been found to provide an effective alternative to rifampicin for the eradication of meningococcal carriage among adults. (3) Ceftriaxone – A single IM injection of 250 mg of ceftriaxone in adult or 125 mg in children may also eradicate meningococcal carriage.

Public enlightenment

Educational programs will be needed to enlighten medical professionals and the general public about the risks of IMD, available vaccines, and means of prevention. One of the effective intervention strategies includes setting up systems in health-care facilities and elucidating the best practices for implementation of vaccine recommendations, including the need for a booster dose of conjugate vaccine and immunization with the new vaccine. IMD is a rapid and unpredictable illness, leaving substantial morbidity and mortality among those who are afflicted. Although implementation of MenACWY immunization recommendations was accompanied by a substantial decrease in the incidence of N. meningitidis infection in adolescents aged 11–18 years, protection was short lived, requiring a booster dose to protect through late adolescence.[17]

The recent outbreaks of meningococcal C disease in Nigeria serve as a lesson to the devastating effects of outbreaks to the community. Therefore, increasing awareness among clinicians and the public regarding meningococcal immunization in high-risk individuals in all age groups and those age groups with the highest disease burden remains essential for success. Finally, there is a need for legislation on housing, waste disposal, and environmental sanitation.

CONCLUSION

IMD is mainly caused by N. meningitidis, usually presenting in form of meningococcemia.[1] The recent advances in molecular genetics and immunological assays have opened new horizons in the understanding of meningococcal disease and its myriad of clinical presentation. Development of tetravalent (A, C, Y, and W135) polysaccharide conjugate vaccines and implementation of mass immunization raises the hope that diseases caused by these serogroups can be controlled in the near future. Meningococcal serogroup C conjugate vaccines have substantially reduced the incidence of serogroup C meningococcal disease in industrialized nations such as the United Kingdom. Therefore, on the basis of the favorable experience with mass immunization with meningococcal serogroup C conjugate vaccines in the United Kingdom, it is expected that tetravalent conjugate vaccines being developed for meningococcal disease associated with serogroups A, C, Y, and W135 will provide improved protection for individuals of all ages.[343536373839]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.