Published: January 2016

What is the problem?

Meningitis is a disease caused by an infection of the meninges, the membranes that surround the brain and spinal cord.1 Meningitis due to bacterial infections can cause death, brain damage, or hearing loss.2

The "meningitis belt," which runs across 26 countries in sub-Saharan Africa, has high rates of both endemic and epidemic bacterial meningitis.3 Group A Neisseria meningitidis bacteria (NmA), which cause Group A meningococcal meningitis (meningitis A), are considered to be the most significant cause of epidemic and endemic meningitis cases in the meningitis belt.4

What is the program?

A meningococcal A conjugate vaccine was developed specifically for the meningitis belt by a partnership between the World Health Organization (WHO) and PATH.5 Mass campaigns to vaccinate all residents of meningitis belt countries between ages 1 and 29 began in 2010.6

In our limited investigation, we found some promising evidence that these mass campaigns may have reduced short-term meningococcal A incidence in some vaccinated populations, though we have not carefully vetted this evidence. For example, we reviewed two studies on mass meningococcal A vaccination campaigns in Chad that found substantial short-term reductions in meningitis incidence that seem attributable to the campaigns.7 In addition, WHO has noted that there have been no meningococcal A epidemics in populations that have received conjugate vaccinations since 2010.8

We have not investigated whether these vaccination campaigns are expected to provide long-term protection against meningitis A.

Who is working on it?

Gavi (www.gavi.org), a large funding vehicle for vaccinations, provided funding for 215 million meningococcal A conjugate vaccinations in mass campaigns in 15 meningitis belt countries between 2010 and 2014.9

We are not aware of any other organizations currently funding meningococcal A conjugate vaccine programs.

Is there room for more funding?

Gavi plans to fund meningococcal A conjugate vaccine mass campaigns, routine infant immunization, and "catch-up" campaigns (for those born after the mass campaigns but before the start of routine infant immunizations) in all 26 meningitis belt countries by 2018.10 Other than these three types of programs, we do not know of any plausibly cost-effective activities related to meningococcal A conjugate vaccination. We have not made much effort to search for other activities because these programs (mass campaigns, “catch-up” campaigns, and routine immunization) seem to be the core programs related to meningococcal A conjugate vaccination.

We have seen a few examples of delayed rollouts of meningitis A vaccination campaigns so far, but it seems likely to us that non-funding constraints caused the delays.11

Overall, it appears unlikely that Gavi requires more funding to fulfill its commitments to these programs. Between 2016 and 2020, Gavi expects to receive ~$9.6 billion (~$7.5 billion of which has already been committed by national governments) and spend ~$9.4 billion.12 Based on this information, the Gavi Secretariat believes that Gavi will be able to fund all of its planned programs between 2016 and 2020.13

Our process

We began investigating meningococcal A conjugate vaccination due to our impression that it could be in the same range of cost-effectiveness as our priority programs. We stopped the investigation after learning that it seems unlikely that there will be room for more funding for this program in the near future.

Sources

Document	Source
Campagne et al. 1999	Source (archive)
Daugla et al. 2014	Source (archive)
Djingarey et al. 2012	Source (archive)
Gamougam et al. 2015	Source (archive)
Gavi annual financial report 2014	Source (archive)
Gavi MenA FAQs 2014	Source (archive)
Gavi Meningitis A vaccine support	Source (archive)
Gavi Meningococcal roadmap 2015	Source (archive)
LaForce and Okwo-Bele 2011	Source (archive)
LaForce et al. 2009	Source (archive)
MedlinePlus Encyclopedia Meningitis 2015	Source (archive)
Molesworth et al. 2002	Source (archive)
WHO Impact of the problem	Source (archive)
WHO Meningococcal meningitis fact sheet 2015	Source (archive)
WHO Weekly epidemiological record No. 13, 2015	Source (archive)

• 1

  "Meningitis is an infection of the membranes covering the brain and spinal cord. This covering is called the meninges." MedlinePlus Encyclopedia Meningitis 2015.

• 2

  "Even when the disease is diagnosed early and adequate treatment is started, 5% to 10% of patients die, typically within 24 to 48 hours after the onset of symptoms. Bacterial meningitis may result in brain damage, hearing loss or a learning disability in 10% to 20% of survivors." WHO Meningococcal meningitis fact sheet 2015.

• 3
  • "Lapeyssonnie first defined the ‘Meningitis Belt’ in 1963, an area between latitudes 4” and 16” north with a high incidence and recurring epidemics which coincided with the 300-1,100-mm mean annual rainfall isohyets south from the Sahara, comprising much of semi-arid sub-Saharan Africa and including the Sahel." Molesworth et al. 2002, Pg 242.
  • "The extended meningitis belt of sub-Saharan Africa, stretching from Senegal in the west to Ethiopia in the east (26 countries), has the highest rates of the disease." WHO Meningococcal meningitis fact sheet 2015.

• 4
  • Campagne et al. 1999 is a study on the epidemiology of bacterial meningitis in Niamey, the capital of the meningitis belt country Niger, between 1981 and 1996. Over the course of 15 years, Neisseria meningitidis bacteria caused 57.7% of cases, and 85.6% of those cases were Serogroup A. Campagne et al. 1999, Pg 499.
  • We have not seen high quality epidemiological studies representing all countries throughout the meningitis belt. However, experts we have read agree that Group A Neisseria meningitidis bacteria are the most significant cause of meningitis in the region, especially for epidemic meningitis:
    • "Epidemic meningitis is a greatly feared disease in sub-Saharan Africa. These epidemics cause death, disability and societal chaos when they occur and have been shown to be an important precipitating cause of poverty in affected families. Despite the use of tens of millions of doses of meningococcal polysaccharide vaccine, meningitis epidemics, largely due to Group A Neisseria meningitidis, continue to plague meningitis belt countries." LaForce et al. 2009, Pg B13.
    • "All districts in Burkina Faso are at risk of meningitis epidemics. The last major meningitis epidemic occurred from 2006 to 2008 and caused over 45,000 cases of meningitis with about 90% of cases due to Group A Neisseria meningitidis (NmA; Fig. 1). Endemic meningococcal disease rates are also high, making meningitis one of the most important public health problems in Burkina Faso." Djingarey et al. 2012, Pg B40.
    • "For >100 years, countries in the meningitis belt of Africa have experienced intermittent epidemics of meningococcal meningitis, caused mainly by the serogroup A meningococcus." Gamougam et al. 2015, Pg 115.

• 5

  "In June 2001, with funding from the Bill & Melinda Gates Foundation, PATH, a Seattle-based NGO, and WHO formed a partnership called the Meningitis Vaccine Project (MVP) with the specific goal of eliminating NmA epidemics by developing, testing, licensing, and introducing an affordable meningococcal A conjugate vaccine for use in the African meningitis belt [3]. Serum Institute of India Ltd. in Pune, India (SIIL), began developing a monovalent meningococcal A conjugate vaccine using a conjugation method originally discovered at the Center for Biologics Evaluation and Research laboratories at the US Food and Drug Administration in Bethesda, USA. Clinical trials of the vaccine were begun in 2005, and after the Drugs Controller General of India granted market authorization for the vaccine in December 2009 the dossier was submitted by SIIL to WHO for prequalification. Given the severity and magnitude of the meningitis problem in sub-Saharan Africa the prequalification of the Men A conjugate vaccine, now called MenAfriVac, was granted “fast track” status by WHO, and after extensive review the vaccine was prequalified in June 2010[3]." Djingarey et al. 2012, Pg B41.

• 6
  • "The first strategy is an initial vaccination campaign of people ages 1–29 (about 70 percent of the total population in these countries) to rapidly establish herd immunity." LaForce and Okwo-Bele 2011, Pg 1052.
  • "Available and prequalified by the WHO since 2010, MenAfriVac has allowed the Gavi strategy to be implemented." @Gavi Meningococcal Roadmap 2015@, Pg 1.

• 7
  • Daugla et al. 2014 used the staggered rollout of the meningococcal A vaccine (PsA-TT) in 2011 and 2012 to observe differences between vaccinated and unvaccinated populations in the same country and year.
    Daugla et al. 2014:
    • "Roughly 1.8 million individuals aged 1–29 years received one dose of PsA–TT during a vaccination campaign in three regions of Chad in and around the capital N’Djamena during 10 days in December, 2011." Pg 40.
    • "In the three regions in which vaccination was undertaken in December, 2011, estimated vaccine coverage was 102%. These regions were chosen for logistical reasons. Nationwide vaccination of the 1-29-year-old population was achieved in three further phases between June and December, 2012, with estimated vaccine coverage of 95%, 95%, and 81%, respectively." Pg 43.
  • While meningitis incidence had followed similar trends in the vaccinated and unvaccinated regions prior to the 2011 campaigns, in the 2012 dry season meningitis only returned to high levels (following the low-incidence wet season) in unvaccinated regions. Observed incidence of all types of meningitis cases in the vaccinated regions was 2.48 per 100,000, and observed incidence in unvaccinated regions was 43.8 per 100,000.
    Daugla et al. 2014:
    • "First, surveillance data suggest that the epidemic was progressing in a similar way in vaccinated and in unvaccinated areas before vaccination…" Pg 45.
    • "The incidence of reported cases of meningitis during the first 26 weeks of 2012 in the three regions where vaccination with PsA-TT of individuals aged 1-29 years had been undertaken the previous year was 2.48 per 100000 (57 cases per 2.3 million population). By contrast, the incidence in areas where PsA-TT vaccination had not been undertaken as part of the mass campaign, including the areas where reactive vaccination was undertaken in response to an outbreak, was 43.8 per 100000 (3809 cases per 8.7 million population), a 94% difference in total incidence in 2012 (p<0.0001)." Pg 43.
    • Figure 3, Pg 43.
  • Gamougam et al. 2015 follows up on the results from Daugla et al. 2014, using the same data sources but including data on meningitis incidence in 2013, after the remaining regions in Chad had been vaccinated. Regions vaccinated in 2012 saw a reduction in overall meningitis incidence very similar to the observed reduction in the previously vaccinated regions, with a decline from 43.8 cases per 100,000 in 2012 to 2.8 per 100,000 in 2013. In the regions vaccinated in 2011, meningitis infections remained at reduced levels, with an observed incidence of 1.1 per 100,000.
    Gamougam et al. 2015:
    • "In the rest of the country, in which vaccination was implemented during 2012 only, meningitis incidence decreased from 43.8/100,000 (3,809/8.7 million) in weeks 1-26 of 2012 to 2.8/100,000 (247/8.7 million) during the same period in 2013, a 96% reduction (p<0.0001)." Pg 115.
    • "Meningitis incidence remained low in the N’Djamena regions in 2013 at 1.1/100,000 (25/2.3 million)." Pg 115.
    • Figure 2, Pg 117.
  • Overall, we find Daugla et al. 2014 and Gamougam et al. 2015's methodology of exploiting the staggered vaccine rollout compelling, even though the choice of districts for the 2011 vaccinations was not randomized. Given the similar rates of meningitis incidence in both groups of districts before mass vaccination began (Daugla et al. 2014, Figure 3), it seems unlikely that such a large difference in meningitis incidence rates in these groups of districts would be due to random chance. Gamougam et al. 2015's observation of similarly large reductions in meningitis rates in previously unvaccinated regions after the 2012 mass campaigns offers more support for this view. However, we have not carefully vetted the methodology of these studies.

• 8

  "Starting in 2010, the progressive introduction of a meningococcal A conjugate vaccine (MACV)1 to the epidemic-prone areas of the 26 countries in the extended African meningitis belt has brought about a dramatic reduction of N.m. A cases, and elimination of N.m. A epidemics in these areas. It is expected that with a high coverage rate among persons aged 1–29 years (i.e. approximately 315 million people), serogroup A meningococcal epidemics will be eliminated from this region of Africa." WHO Weekly epidemiological record No. 13, 2015, Pg 124.

• 9

  "From 2010 to 2014, Gavi-supported meningitis A vaccine campaigns reached over 215 million children and young adults in 15 countries in the 'meningitis belt', which stretches across 26 countries in Africa. Those supported so far are Benin, Burkina Faso, Cameroon, Chad, Côte d’Ivoire, Ethiopia, Gambia, Ghana, Mali, Mauritania, Niger, Nigeria, Senegal, Gambia, and Togo." Gavi Meningitis A vaccine support.

• 10
  • @Gavi meningococcal roadmap 2015@:
    • "Gavi committed to fund in 26 Gavi-eligible countries in the “meningitis belt” of Africa, (1) preventative vaccination campaigns, (2) routine immunisation, (3) catch-up vaccination campaigns to immunise the children born between the start of campaign vaccinations and the start of routine immunisations, and (4) maintenance of a vaccine stockpile for emergency response." Pg 1.
    • "Gavi support to campaign vaccination is planned to end when all 26 target countries will have rolled out routine immunisation and when meningococcal meningitis epidemics are eliminated as a public health problem in Africa. If current epidemiological trends continue, this will occur in 2018 after which routine immunisation is expected to keep MenA disease under control. Thereafter, Gavi funding for meningococcal routine immunisation will continue to be made available to eligible countries requesting such support." Pg 1.
  • Gavi Meningitis A vaccine support:
    • "From 2010 to 2014, Gavi-supported meningitis A vaccine campaigns reached over 215 million children and young adults in 15 countries in the “meningitis belt”, which stretches across 26 countries in Africa. Those supported so far are Benin, Burkina Faso, Cameroon, Chad, Côte d’Ivoire, Ethiopia, Gambia, Ghana, Mali, Mauritania, Niger, Nigeria, Senegal, Gambia, and Togo."
    • "The remaining 11 countries in the meningitis belt are expected to conduct campaigns in 2017/2018, vaccinating over 260 million people."

• 11
  • WHO's list of countries with mass campaign rollouts by the end of 2014 largely matches the initial rollout plan published in 2011, with the exceptions of Democratic Republic of the Congo, South Sudan, and Guinea, which were behind schedule. Mauritania's rollout appears to have been started ahead of schedule.
    • "Overall the campaigns reached >64 million individuals in 2014, bringing the total number of persons vaccinated in the African meningitis belt to >217 million in 15 countries (Benin, Burkina Faso, Cameroon, Chad, Côte d’Ivoire, Ethiopia, Gambia, Ghana, Mali, Mauritania, Niger, Nigeria, Senegal, Sudan and Togo)." WHO Weekly epidemiological record No. 13, 2015, Pg 125.
    • In 2011, WHO's proposed rollout plan scheduled Burkina Faso, Niger, Mali, Nigeria, Chad, North Sudan, Ghana, Benin, Ethiopia, Cameroon, Democratic Republic of the Congo, South Sudan, Senegal, Côte d’Ivoire, Togo, Guinea, and The Gambia to have started mass campaigns by the end of 2014. LaForce and Okwo-Bele 2011, Exhibit 2, Pg 1054.
  • WHO notes that the Ebola outbreak caused delays in Guinea, and that political unrest caused delays in South Sudan. We are uncertain what may have caused delays in Democratic Republic of the Congo, but in November 2014 Gavi noted that the country had not yet applied for funding.
    • "The campaign initially planned in Guinea was postponed due to the Ebola epidemic during 2014. The campaign in South Sudan was postponed to 2015 due to the political unrest in the country." WHO Weekly epidemiological record No. 13, 2015, Pg 125.
    • "The 9 countries that are still to apply for mass preventive campaigns include: Burundi, Central African Republic, Democratic Republic of Congo, Eritrea, Guinea Bissau, Kenya, Rwanda, Tanzania and Uganda." Gavi MenA FAQs 2014.

• 12

  Gavi annual financial report 2014:

  • "At a pledging conference hosted by German Chancellor Angela Merkel in Berlin, world leaders came together to accelerate access to vaccines in the world’s poorest countries. The new pledges, totalling US$7.539 billion for the period 2016 to 2020, will enable countries to immunise an additional 300 million children, leading to 5 to 6 million premature deaths being averted and economic benefits of between US$80 billion and US$ 100 billion for developing countries through productivity gains and savings in treatment and transportation costs and caretaker wages." Pg 17.
  • Future cash flows table, Pg 18.

• 13

  "After taking into account available cash and investments, and assuming that the forecasted level of funding for 2016 to 2018 will be maintained through 2020, the Secretariat forecasts that Gavi will have sufficient resources to fund all its programmatic commitments through 2020." Gavi annual financial report 2014, Pg 18.