Expansion of Neisseria meningitidis Serogroup C Clonal Complex 10217 during Meningitis Outbreak, Burkina Faso, 2019.

During January 28-May 5, 2019, a meningitis outbreak caused by Neisseria meningitidis serogroup C (NmC) occurred in Burkina Faso. Demographic and laboratory data for meningitis cases were collected through national case-based surveillance. Cerebrospinal fluid was collected and tested by culture and real-time PCR. Among 301 suspected cases reported in 6 districts, N. meningitidis was the primary pathogen detected; 103 cases were serogroup C and 13 were serogroup X. Whole-genome sequencing revealed that 18 cerebrospinal fluid specimens tested positive for NmC sequence type (ST) 10217 within clonal complex 10217, an ST responsible for large epidemics in Niger and Nigeria. Expansion of NmC ST10217 into Burkina Faso, continued NmC outbreaks in the meningitis belt of Africa since 2019, and ongoing circulation of N. meningitidis serogroup X in the region underscore the urgent need to use multivalent conjugate vaccines in regional mass vaccination campaigns to reduce further spread of those serogroups.

Trends in Neisseria meningitidis serogroups amongst patients with suspected cerebrospinal meningitis in the meningitis belt of Ghana: a 5-year retrospective study.

BACKGROUND: Serogroup A Neisseria meningitidis was the major cause of meningococcal meningitis epidemics in the African meningitis belt before 2010 when the monovalent meningococcal A conjugate vaccine (MenAfriVac) was introduced in the region. Therefore, this study aimed to establish the trends in N. meningitidis serogroups from 2016 to 2020 in Ghana's meningitis belt. METHODS: Polymerase chain reaction (PCR) confirmed laboratory results of suspected cases of cerebrospinal meningitis from January, 2016 to March, 2020 were obtained from the Tamale Public Health Laboratory. The data were subjected to trend analysis using Statistical Package for the Social Sciences version 25. Differences between discrete variables were analyzed using the Cochran-Armitage trend test. RESULTS: Of the 2,426 suspected cases, 395 (16.3%) were confirmed positive for N. meningitidis using PCR. Serogroup X showed a significant upward trend (P < 0.01), and serogroup W showed a downward trend (P < 0.01). However, no significant trend was observed for any other serogroup. CONCLUSION: This study showed the emergence of serogroup X, a non-vaccine type, as the predominant N. meningitidis serogroup in the wake of a declining serogroup W in Ghana's meningitis belt.

Toward Establishing Integrated, Comprehensive, and Sustainable Meningitis Surveillance in Africa to Better Inform Vaccination Strategies.

Large populations across sub-Saharan Africa remain at risk of devastating acute bacterial meningitis epidemics and endemic disease. Meningitis surveillance is a cornerstone of disease control, essential for describing temporal changes in disease epidemiology, the rapid detection of outbreaks, guiding vaccine introduction and monitoring vaccine impact. However, meningitis surveillance in most African countries is weak, undermined by parallel surveillance systems with little to no synergy and limited laboratory capacity. African countries need to implement comprehensive meningitis surveillance systems to adapt to the rapidly changing disease trends and vaccine landscapes. The World Health Organization and partners have developed a new investment case to restructure vaccine-preventable disease surveillance. With this new structure, countries will establish comprehensive and sustainable meningitis surveillance systems integrated with greater harmonization between population-based and sentinel surveillance systems. There will also be stronger linkage with existing surveillance systems for vaccine-preventable diseases, such as polio, measles, yellow fever, and rotavirus, as well as with other epidemic-prone diseases to leverage their infrastructure, transport systems, equipment, human resources and funding. The implementation of these concepts is currently being piloted in a few countries in sub-Saharan Africa with support from the World Health Organization and other partners. African countries need to take urgent action to improve synergies and coordination between different surveillance systems to set joint priorities that will inform action to control devastating acute bacterial meningitis effectively.

An overview of bacterial meningitis epidemics in Africa from 1928 to 2018 with a focus on epidemics "outside-the-belt".

BACKGROUND: Bacterial meningitis occurs worldwide but Africa remains the most affected continent, especially in the "Meningitis belt" that extends from Senegal to Ethiopia. Three main bacteria are responsible for causing bacterial meningitis, i.e., N. meningitidis (Nm), S. pneumoniae and H. influenzae type b. Among Nm, serogroup A used to be responsible for up to 80 to 85% of meningococcal meningitis cases in Africa. Since 2000, other Nm serogroups including W, X and C have also been responsible for causing epidemics. This overview aims to describe the main patterns of meningitis disease cases and pathogens from 1928 to 2018 in Africa with a special focus on disease conditions "out-of-the-belt" area that is still usually unexplored. Based on basic spatio-temporal methods, and a 90-years database of reported suspected meningitis cases and death from the World Health Organization, we used both geographic information system and spatio-temporal statistics to identify the major localizations of meningitis epidemics over this period in Africa. RESULTS: Bacterial meningitis extends today outside its historical limits of the meningitis belt. Since the introduction of MenAfrivac vaccine in 2010, there has been a dramatic decrease in NmA cases while other pathogen species and Nm variants including NmW, NmC and Streptococcus pneumoniae have become more prevalent reflecting a greater diversity of bacterial strains causing meningitis epidemics in Africa today. CONCLUSION: Bacterial meningitis remains a major public health problem in Africa today. Formerly concentrated in the region of the meningitis belt with Sub-Saharan and Sudanian environmental conditions, the disease extends now outside these historical limits to reach more forested regions in the central parts of the continent. With global environmental changes and massive vaccination targeting a unique serogroup, an epidemiological transition of bacterial meningitis is ongoing, requiring both a better consideration of the etiological nature of the responsible agents and of their proximal and distal determinants.

Invasive Meningococcal Disease in Africa's Meningitis Belt: More Than Just Meningitis?

Since the progressive introduction of the meningococcal serogroup A conjugate vaccine within Africa's meningitis belt beginning in 2010, the burden of meningitis due to Neisseria meningitidis serogroup A (NmA) has substantially decreased. Non-A serogroups C/W/X are now the most prevalent. Surveillance within the belt has historically focused on the clinical syndrome of meningitis, the classic presentation for NmA, and may not adequately capture other presentations of invasive meningococcal disease (IMD). The clinical presentation of infection due to serogroups C/W/X includes nonmeningeal IMD, and there is a higher case-fatality ratio associated with these non-A serogroups; however, data on the nonmeningeal IMD burden within the belt are scarce. Expanding surveillance to capture all cases of IMD, in accordance with the World Health Organization's updated vaccine-preventable disease surveillance standards and in preparation for the anticipated introduction of a multivalent meningococcal conjugate vaccine within Africa's meningitis belt, will enhance meningococcal disease prevention across the belt.

Epidemiology of Bacterial Meningitis in the Nine Years Since Meningococcal Serogroup A Conjugate Vaccine Introduction, Niger, 2010-2018.

BACKGROUND: In 2010, Niger and other meningitis belt countries introduced a meningococcal serogroup A conjugate vaccine (MACV). We describe the epidemiology of bacterial meningitis in Niger from 2010 to 2018. METHODS: Suspected and confirmed meningitis cases from January 1, 2010 to July 15, 2018 were obtained from national aggregate and laboratory surveillance. Cerebrospinal fluid specimens were analyzed by culture and/or polymerase chain reaction. Annual incidence was calculated as cases per 100 000 population. Selected isolates obtained during 2016-2017 were characterized by whole-genome sequencing. RESULTS: Of the 21 142 suspected cases of meningitis, 5590 were confirmed: Neisseria meningitidis ([Nm] 85%), Streptococcus pneumoniae ([Sp] 13%), and Haemophilus influenzae ([Hi] 2%). No NmA cases occurred after 2011. Annual incidence per 100 000 population was more dynamic for Nm (0.06-7.71) than for Sp (0.18-0.70) and Hi (0.01-0.23). The predominant Nm serogroups varied over time (NmW in 2010-2011, NmC in 2015-2018, and both NmC and NmX in 2017-2018). Meningococcal meningitis incidence was highest in the regions of Niamey, Tillabery, Dosso, Tahoua, and Maradi. The NmW isolates were clonal complex (CC)11, NmX were CC181, and NmC were CC10217. CONCLUSIONS: After MACV introduction, we observed an absence of NmA, the emergence and continuing burden of NmC, and an increase in NmX. Niger's dynamic Nm serogroup distribution highlights the need for strong surveillance programs to inform vaccine policy.

Eliminating Meningococcal Epidemics From the African Meningitis Belt: The Case for Advanced Prevention and Control Using Next-Generation Meningococcal Conjugate Vaccines.

The introduction and rollout of a meningococcal serogroup A conjugate vaccine, MenAfriVac, in the African meningitis belt has eliminated serogroup A meningococcal infections for >300 million Africans. However, serogroup C, W, and X meningococci continue to circulate and have been responsible for focal epidemics in meningitis belt countries. Affordable multivalent meningococcal conjugate vaccines are being developed to prevent these non-A epidemics. This article describes the current epidemiologic situation and status of vaccine development and highlights questions to be addressed to most efficiently use these new vaccines.

MenAfriNet: A Network Supporting Case-Based Meningitis Surveillance and Vaccine Evaluation in the Meningitis Belt of Africa.

Meningococcal meningitis remains a significant public health threat, especially in the African meningitis belt where Neisseria meningitidis serogroup A historically caused large-scale epidemics. With the rollout of a novel meningococcal serogroup A conjugate vaccine (MACV) in the belt, the World Health Organization recommended case-based meningitis surveillance to monitor MACV impact and meningitis epidemiology. In 2014, the MenAfriNet consortium was established to support strategic implementation of case-based meningitis surveillance in 5 key countries: Burkina Faso, Chad, Mali, Niger, and Togo. MenAfriNet aimed to develop a high-quality surveillance network using standardized laboratory and data collection protocols, develop sustainable systems for data management and analysis to monitor MACV impact, and leverage the surveillance platform to perform special studies. We describe the MenAfriNet consortium, its history, strategy, implementation, accomplishments, and challenges.

A New Sequence Type of Neisseria meningitidis Serogroup C Associated With a 2016 Meningitis Outbreak in Mali.

In 2016, Mali reported a bacterial meningitis outbreak consisting of 39 suspected cases between epidemiologic weeks 9 and 17 with 15% case fatality ratio in the health district of Ouéléssebougou, 80 kilometers from the capital Bamako. Cerebrospinal fluid specimens from 29 cases were tested by culture and real-time polymerase chain reaction; 22 (76%) were positive for bacterial meningitis pathogens, 16 (73%) of which were Neisseria meningitidis (Nm). Of the Nm-positive specimens, 14 (88%) were N meningitidis serogroup C (NmC), 1 was NmW, and 1 was nongroupable. Eight NmC isolates recovered by culture from the outbreak were characterized using whole genome sequencing. Genomics analysis revealed that all 8 isolates belonged to a new sequence type (ST) 12446 of clonal complex 10217 that formed a distinct clade genetically similar to ST-10217, a NmC strain that recently caused large epidemics of meningitis in Niger and Nigeria. The emergence of a new ST of NmC associated with an outbreak in the African meningitis belt further highlights the need for continued molecular surveillance in the region.

Bacterial Meningitis Epidemiology in Five Countries in the Meningitis Belt of Sub-Saharan Africa, 2015-2017.

BACKGROUND: The MenAfriNet Consortium supports strategic implementation of case-based meningitis surveillance in key high-risk countries of the African meningitis belt: Burkina Faso, Chad, Mali, Niger, and Togo. We describe bacterial meningitis epidemiology in these 5 countries in 2015-2017. METHODS: Case-based meningitis surveillance collects case-level demographic and clinical information and cerebrospinal fluid (CSF) laboratory results. Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzae cases were confirmed and N. meningitidis/H. influenzae were serogrouped/serotyped by real-time polymerase chain reaction, culture, or latex agglutination. We calculated annual incidence in participating districts in each country in cases/100 000 population. RESULTS: From 2015-2017, 18 262 suspected meningitis cases were reported; 92% had a CSF specimen available, of which 26% were confirmed as N. meningitidis (n = 2433; 56%), S. pneumoniae (n = 1758; 40%), or H. influenzae (n = 180; 4%). Average annual incidences for N. meningitidis, S. pneumoniae, and H. influenzae, respectively, were 7.5, 2.5, and 0.3. N. meningitidis incidence was 1.5 in Burkina Faso, 2.7 in Chad, 0.4 in Mali, 14.7 in Niger, and 12.5 in Togo. Several outbreaks occurred: NmC in Niger in 2015-2017, NmC in Mali in 2016, and NmW in Togo in 2016-2017. Of N. meningitidis cases, 53% were NmC, 30% NmW, and 13% NmX. Five NmA cases were reported (Burkina Faso, 2015). NmX increased from 0.6% of N. meningitidis cases in 2015 to 27% in 2017. CONCLUSIONS: Although bacterial meningitis epidemiology varied widely by country, NmC and NmW caused several outbreaks, NmX increased although was not associated with outbreaks, and overall NmA incidence remained low. An effective low-cost multivalent meningococcal conjugate vaccine could help further control meningococcal meningitis in the region.