Claims-based algorithm to estimate the Expanded Disability Status Scale for multiple sclerosis in a German health insurance fund: a validation study using patient medical records.

Background: The Expanded Disability Status Scale (EDSS) quantifies disability and measures disease progression in multiple sclerosis (MS), however is not available in administrative claims databases. Objectives: To develop a claims-based algorithm for deriving EDSS and validate it against a clinical dataset capturing true EDSS values from medical records. Methods: We built a unique linked dataset combining claims data from the German AOK PLUS sickness fund and medical records from the Multiple Sclerosis Management System 3D (MSDS3D). Data were deterministically linked based on insurance numbers. We used 69 MS-related diagnostic indicators recorded with ICD-10-GM codes within 3 months before and after recorded true EDSS measures to estimate a claims-based EDSS proxy (pEDSS). Predictive performance of the pEDSS was assessed as an eight-fold (EDSS 1.0-7.0, ≥8.0), three-fold (EDSS 1.0-3.0, 4.0-5.0, ≥6.0), and binary classifier (EDSS <6.0, ≥6.0). For each classifier, predictive performance measures were determined, and overall performance was summarized using a macro F1-score. Finally, we implemented the algorithm to determine pEDSS among an overall cohort of patients with MS in AOK PLUS, who were alive and insured 12 months prior to and after index diagnosis. Results: We recruited 100 people with MS insured by AOK PLUS who had ≥1 EDSS measure in MSDS3D between 01/10/2015 and 30/06/2019 (620 measurements overall). Patients had a mean rescaled EDSS of 3.2 and pEDSS of 3.0. The pEDSS deviated from the true EDSS by 1.2 points, resulting in a mean squared error of prediction of 2.6. For the eight-fold classifier, the macro F1-score of 0.25 indicated low overall predictive performance. Broader severity groupings were better performing, with the three-fold and binary classifiers for severe disability achieving a F1-score of 0.68 and 0.84, respectively. In the overall AOK PLUS cohort (3,756 patients, 71.9% female, mean 51.9 years), older patients, patients with progressive forms of MS and those with higher comorbidity burden showed higher pEDSS. Conclusion: Generally, EDSS was underestimated by the algorithm as mild-to-moderate symptoms were poorly captured in claims across all functional systems. While the proxy-based approach using claims data may not allow for granular description of MS disability, broader severity groupings show good predictive performance.

Anti-SARS-CoV-2 monoclonal antibodies for the treatment of mild-to-moderate COVID-19 in multiple sclerosis: A retrospective cohort study.

BACKGROUND: The use and potential benefit of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in people living with multiple sclerosis (pwMS) remains poorly studied. The objective of this study is to describe the therapeutic use of anti-SARS-CoV-2 mAbs among pwMS. METHODS: This retrospective cohort study used electronic medical records data from the TriNetX Dataworks USA Network and included adult pwMS, diagnosed with COVID-19, who received anti-SARS-CoV-2 mAbs in the outpatient setting between November 2020 and April 2022. We analyzed COVID-19 severity at anti-SARS-CoV-2 mAb initiation and up to 30 days, stratified by before/after emergence of Omicron variant and by disease-modifying therapy (DMT). RESULTS: The study included 434 pwMS treated with anti-SARS-CoV-2 mAbs for mild-to-moderate COVID-19, including 270 patients before and 174 after Omicron emergence. Most pwMS were female (80.2%), mean age (SD) was 51.5 (12.5) years. Two-hundred-and-five patients were on DMTs, 51% of whom received anti-CD20s. One patient with moderate COVID-19 was hospitalized whilst receiving glatiramer acetate. No patients required intensive care and there were no deaths. COVID-19 outcomes were comparable following anti-SARS-CoV-2 mAb therapy in patients receiving different DMTs. CONCLUSION: Anti-SARS-CoV-2 mAb treatment for pwMS with mild-to-moderate COVID-19 may reduce the risk of COVID-19-related hospitalization and death.

The socioeconomic impact of disability progression in multiple sclerosis: A retrospective cohort study of the German NeuroTransData (NTD) registry.

Background: Multiple sclerosis (MS) is a progressively debilitating neurologic disease that poses significant costs to the healthcare system and workforce. Objective: To evaluate the impact of MS disease progression on societal costs and quality of life (QoL) using data from the German NeuroTransData (NTD) MS registry. Methods: Cross-sectional cohort study. The cost cohort included patients with MS disability assessed using Expanded Disability Status Scale (EDSS) in 2019 while the QoL cohort included patients assessed using EDSS and EuroQol-5 Dimension 5-Levels between 2009 and 2019. Direct and indirect medical, and non-medical resource use was quantified and costs derived from public sources. Results: Within the QoL cohort (n = 9821), QoL worsened with increasing EDSS. Within the cost cohort (n = 7286), increasing resource use with increasing EDSS was observed. Societal costs per patient, excluding or including disease-modifying therapies, increased from €5694 or €19,315 at EDSS 0 to 3.5 to €25,419 or €36,499 at EDSS 4 to 6.5, and €52,883 or €58,576 at EDSS 7 to 9.5. In multivariate modeling, each 0.5-step increase in EDSS was significantly associated with increasing costs, and worsening QoL. Conclusion: This study confirms the major socioeconomic burden associated with MS disability progression. From a socioeconomic perspective, delaying disability progression may benefit patients and society.

Electronic health record data for assessing risk of hospitalization for COVID-19: Methodological considerations applied to multiple sclerosis.

INTRODUCTION: During the COVID-19 pandemic, electronic health record (EHR) data has been used to investigate disease severity and risk factors for severe COVID-19 in people with multiple sclerosis (pwMS). Methodological challenges including sampling bias, and residual confounding should be considered when conducting EHR-based studies. We aimed to address these limitations related to the use of EHR data in order to identify risk factors, including the use of disease modifying therapies (DMTs), associated with hospitalization for COVID-19 amongst pwMS. METHODS: We performed a retrospective cohort study including a sample of 47,051 pwMS using a large US-based EHR and claims linked database. Follow-up started at the beginning of the pandemic, February 20th 2020, and continued until September 30th 2020. COVID-19 diagnosis was determined by the presence of ICD-10 diagnostic code for COVID-19, or a positive diagnostic laboratory test, or an ICD-10 diagnostic code for coronaviruses. We used Cox regression modeling to assess the impact of baseline demographics, MS disease history and pre-existing comorbidities on the risk of hospitalization for COVID-19. Then, we identified 5,169 pwMS using ocrelizumab (OCR) and 3,351 pwMS using dimethyl fumarate (DMF) at baseline, and evaluated the distribution of the identified COVID-19 risk factors between the two groups. Finally, we used Cox regression models, adjusted for the identified confounders, to estimate the risk of hospitalization for COVID-19 in pwMS treated with OCR compared to DMF. RESULTS: Among the pwMS cohort, we identified 799 COVID-19 cases (1.7%) which resulted in 182 hospitalizations for COVID-19 (0.4%). Population differences between the pwMS and COVID-19 cohorts were observed. Statistical modeling identified older age, male gender, African-American race, walking with assistance, non-ambulatory status, severe relapse requiring hospitalization in year prior to baseline, and specific comorbidities to be associated with a higher risk of COVID-19 related-hospitalization. Comparing the COVID-19 risk factors between OCR users and DMF users, MS characteristics including ambulatory status and MS subtype were highly imbalanced, likely arising from key differences in the labelled indications for these therapies. Compared to DMF use, in unadjusted (HR 1.58, 95% CI 0.73 - 3.44), adjusted (HR 1.28, 95% CI 0.58 - 2.83), propensity score weighted (HR 1.25, 95% CI 0.56 - 2.80), and doubly robust models (HR 1.29, 95% CI 0.57 - 2.89), no significantly increased risk of hospitalization for COVID-19 was associated with OCR use. CONCLUSION: We observed significant population differences when comparing all pwMS to COVID-19 cases, as well as significant differences in key confounders between OCR and DMF treated patients. In unadjusted analyses we did not observe a statistically significant higher risk of COVID-19 hospitalization in pwMS treated with OCR compared to DMF, with further attenuation of risk when adjusting for the key confounders. This study re-emphasises the importance to appropriately consider both sampling and confounding bias in EHR-based MS research.

Serious infections in patients with relapsing and progressive forms of multiple sclerosis: A German claims data study.

BACKGROUND: People with multiple sclerosis (pwMS) have a higher risk of serious infection (i.e., infection-related hospitalizations) than people without MS. Few studies have explored the risk of serious infections by MS phenotype in a real-world setting. This retrospective study compared the incidence of serious infections among people with relapse remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). METHODS: Adult pwMS were selected from a German claims database, based on one inpatient or two outpatient diagnoses of MS (ICD-10 G35) by a neurologist from 01/01/2016 to 12/31/2018. Three cohorts (RRMS, PPMS, SPMS) were identified based on codes for MS subtypes included in the German Modification of the ICD-10 system. A fourth cohort of unspecified MS patients combined those with conflicting MS subtype diagnoses and multiple unspecified codes for MS. Serious infections were defined as hospitalizations for which infections were selected as the primary inpatient diagnosis. Infections were identified from a basket of ICD-10 codes distributed across 11 main categories, according to possible pathogen (e.g., other bacterial diseases [A30-A49]) or anatomical location (e.g., urinary tract infection [N39.0]). Multiple infections were counted if an interval of at least 60 days was recorded between episodes. Serious infections were counted from index (i.e., first recorded MS code) until the end of the study period or death. Incidence rates (IRs) were reported per 100 patient years (PY). RESULTS: A total of 4,250 pwMS (RRMS: 2,307, PPMS: 282, SPMS: 558, unspecified MS: 1,135) were included; 32 patients progressed from RRMS to SPMS during the follow-up period. Mean (SD) age at baseline was 46.6 (13.6), 61.9 (12.4), and 62.5 (11.8) years in patients with RRMS, PPMS, and SPMS, respectively. Most pwMS were female (RRMS 74.8%, PPMS 62.1%, SPMS 67.4%). Progressive pwMS were more likely to have at least 1 comorbidity (PPMS 87.2%, SPMS 87.5%) compared to those with relapsing MS (61.9%). Most RRMS patients received disease-modifying therapy during follow-up (82.1%), while less than half of progressive MS patients did (PPMS 23.8%, SPMS 31.4%). Over a mean (SD) follow-up period of 3.5 (0.8) years, the IR of serious infections per 100 PY was higher in progressive MS cohorts (PPMS 13.5 [11.3-16.1], SPMS 13.6 [12.0-15.3]) than in the RRMS group (3.4 [3.0-3.7]). Yearly IRs remained stable over time in each cohort. Where anatomical location was specified, respiratory (2.0 per 100 PY) and genitourinary (1.9 per 100 PY) infections were most common. Across all subtypes, higher rates of serious infections were observed in men and older patients. CONCLUSION: Progressive MS, older age and male sex are associated with an increased risk of serious infections. Overall, respiratory and genitourinary infections were the most commonly reported serious infections.

Anti-SARS-CoV-2 T-stem cell memory persists in ocrelizumab-treated MS patients.

BACKGROUND: Development of long-lasting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) T-cell responses in persons with multiple sclerosis (pwMS) treated with ocrelizumab is questioned. OBJECTIVE: Investigate antiviral T-cell responses after infection with SARS-CoV-2 in ocrelizumab-treated pwMS. Control groups included ocrelizumab-treated pwMS without SARS-CoV-2 infection, and non-MS individuals with and without SARS-CoV-2 infection. METHODS: Peripheral blood mononuclear cells were stimulated with SARS-CoV-2 peptide pools and T-cell reactivity was assessed by ELISPOT for interferon (IFN)-γ detection, and by multiparametric fluorescence-activated cell sorting (FACS) analyses for assessment and characterization of T-cell activation. RESULTS: ELISPOT assay against the spike and the N protein of SARS-CoV-2 displayed specific T-cell reactivity in 28/29 (96%) pwMS treated with ocrelizumab and infected by SARS-CoV-2, similar to infected persons without MS. This reactivity was present 1 year after infection and independent from the time of ocrelizumab infusion. FACS analysis following stimulation with SARS-CoV-2 peptide pools showed the presence of activation-induced markers (AIMs) in both CD4+ and CD8+ T-cell subsets in 96% and 92% of these individuals, respectively. Within naïve AIM+ CD4+ and CD8+ T-cells, we detected T memory stem cells, suggesting the acquisition of long-term memory. CONCLUSIONS: B-cell depletion using ocrelizumab does not impair the development of long-lasting anti-SARS-CoV-2 T-cell responses.

Safety, Adherence and Persistence in a Real-World Cohort of German MS Patients Newly Treated With Ocrelizumab: First Insights From the CONFIDENCE Study.

Background: Real-world relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS) populations may be more diverse than in clinical trials. Here, we present a first analysis of safety, adherence and persistence data from a real-world cohort of patients newly treated with ocrelizumab. Methods: CONFIDENCE (ML39632, EUPAS22951) is an ongoing multicenter, non-interventional post authorization safety study assessing patients with RMS or PPMS newly treated with ocrelizumab or other disease-modifying therapies for up to 10 years. For this analysis, patients newly treated with ocrelizumab were analyzed in subgroups by MS phenotype and age over a mean ~1 year of exposure totaling 2,329 patient years [PY]). Results: At data cutoff (14 October 2020), 1,702 patients with RMS and 398 patients with PPMS were treated with ≥1 dose of ocrelizumab. At baseline, the mean ages (SD) of patients with RMS and PPMS were 41.59 (11.24) and 50.95 (9.88) years and the mean EDSS (Expanded Disability Status Scale) was 3.18 (1.87) and 4.41 (1.59), respectively. The most common adverse events (AEs) and serious AEs across both phenotypes were infections and infestations, with infection SAE rates of 2.8 events/100 PY and 1.5 events/100 PY in patients with RMS and PPMS, respectively. Across all phenotypes, ocrelizumab persistence was 92% at 24 months; median time between doses was ~6 months. Conclusions: The ocrelizumab safety profile observed in the CONFIDENCE real-world MS population was consistent to the one observed in pivotal clinical trials. High treatment persistence and adherence were observed. Trial Registration: ML39632, EUPAS22951.

Risk of requiring a wheelchair in primary progressive multiple sclerosis: Data from the ORATORIO trial and the MSBase registry.

BACKGROUND AND PURPOSE: Reaching Expanded Disability Status Scale (EDSS) ≥7.0 represents the requirement for a wheelchair. Here we (i) assess the effect of ocrelizumab on time to EDSS ≥7.0 over the ORATORIO (NCT01194570) double-blind and extended controlled periods (DBP+ECP), (ii) quantify likely long-term benefits by extrapolating results, and (iii) assess the plausibility of extrapolations using an independent real-world cohort (MSBase registry; ACTRN12605000455662). METHODS: Post hoc analyses assessing time to 24-week confirmed EDSS ≥7.0 in two cohorts of patients with primary progressive multiple sclerosis (baseline EDSS 3.0-6.5) were investigated in ORATORIO and MSBase. RESULTS: In the ORATORIO DBP+ECP, ocrelizumab reduced the risk of 24-week confirmed EDSS ≥7.0 (hazard ratio = 0.54, 95% confidence interval [CI]: 0.31-0.92; p = 0.022). Extrapolated median time to 24-week confirmed EDSS ≥7.0 was 12.1 and 19.2 years for placebo and ocrelizumab, respectively (7.1-year delay [95% CI: -4.3 to 18.4]). In MSBase, the median time to 24-week confirmed EDSS ≥7.0 was 12.4 years. CONCLUSIONS: Compared with placebo, ocrelizumab significantly delayed time to 24-week confirmed wheelchair requirement in ORATORIO. The plausibility of the extrapolated median time to reach this milestone in the placebo group was supported by observed real-world data from MSBase. Extrapolated benefits for ocrelizumab over placebo could represent a truly meaningful delay in loss of ambulation and independence.

Adolescents and adults with Fontan circulation: insights from the PREpArE-Fontan registry.

The Patient Registry for Adolescents and Adults with Stable Fontan Circulation aims to describe a contemporary cohort of Fontan patients who could be eligible for a clinical trial investigating macitentan, an endothelin receptor antagonist. This international, non-interventional, multicentre, cross-sectional, observational registry enrolled patients with "stable" Fontan circulation ≥10 years following extra-cardiac conduit or lateral tunnel procedure. Main exclusion criteria were NYHA functional class IV, reoperation of Fontan circulation, or signs of disease worsening. Patient characteristics at enrolment are described; available data were collected during a single registration visit. Of the 266 screened patients, 254 were included in this analysis. At enrolment, median (interquartile range) age was 24 (20;30) years, 37%/63% of patients were from the USA/Europe, 54% were male, 54%/47% had undergone extra-cardiac conduit/lateral tunnel procedures, and 95% were in NYHA functional class I or II. History of arrhythmia was more common in older patients and patients with lateral tunnel; overall prevalence was 19%. Most laboratory values were within the normal range but mean creatinine clearance was abnormally low (87.7 ml/min). Angiotensin-converting enzyme inhibitors were used by 48% of patients and their use was associated with creatinine clearance <90 ml/min (p = 0.007), as was Fontan completion at an older age (p = 0.007). 53.4% of patients had clinical characteristics that could potentially meet an endothelin receptor antagonist trial's eligibility criteria. The PREpArE-Fontan registry describes a cohort of patients who could potentially participate in an endothelin receptor antagonist trial and identified early subtle signs of Fontan failure, even in "stable" patients.

Understanding the impacts of COVID-19 pandemic in people with multiple sclerosis treated with ocrelizumab.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to major challenges in the therapeutic management of patients living with multiple sclerosis (PLwMS), particularly regarding the use of disease-modifying therapies. Despite an extraordinary scientific effort to study SARS-CoV-2 in PLwMS, the heterogeneity of COVID-19 manifestations, immunological mechanisms induced by the natural infection or the vaccines, and the extent of protection through the vaccines, major knowledge gaps remain. Here, we describe the scientific evidence generation plan developed by Roche/Genentech to better understand the impact of the COVID-19 pandemic in PLwMS treated with the B-cell depleting monoclonal antibody ocrelizumab.

Five-Year outcomes of patients enrolled in the REVEAL Registry.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare, severe disease characterized by worsening right-sided heart failure, decreasing functional status, and poor survival. The present study characterizes the 5-year survival in the United States of a new and previous diagnosis of PAH in patients stratified by baseline functional class (FC). The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) is a 55-center observational US registry of the demographics, disease course, and management of patients with World Health Organization (WHO) group 1 PAH. METHODS: The REVEAL Registry enrolled newly and previously diagnosed patients aged ≥ 3 months with WHO group 1 PAH consecutively from March 2006 to December 2009. Demographics, disease characteristics, and hemodynamic data were collected at enrollment. Survival analysis was conducted by FC and other subgroups in patients aged ≥ 18 years. RESULTS: Survival differences between previously diagnosed and newly diagnosed patients at 1 year (90.4% vs 86.3%) were maintained to 5 years; 5-year survival for previously diagnosed patients was 65.4% compared with 61.2% for newly diagnosed patients. Previously diagnosed patients in FC I, II, III, and IV had an estimated 5-year survival rate of 88.0%, 75.6%, 57.0%, and 27.2%, respectively, compared with 72.2%, 71.7%, 60.0%, and 43.8% for newly diagnosed patients in FC I, II, III, and IV, respectively. CONCLUSIONS: Patient survival of advanced PAH remains poor at 5 years despite treatment advances. New York Heart Association FC remains one of the most important predictors of future survival. These observations reinforce the importance of continuous monitoring of FC in patients with PAH. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.

Validation of two predictive models for survival in pulmonary arterial hypertension.

The French Pulmonary Hypertension Network (FPHN) registry and the Registry to Evaluate Early And Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) have developed predictive models for survival in pulmonary arterial hypertension (PAH). In this collaboration, we assess the external validity (or generalisability) of the FPHN ItinérAIR-HTAP predictive equation and the REVEAL risk score calculator. Validation cohorts approximated the eligibility criteria defined for each model. The REVEAL cohort comprised 292 treatment-naïve, adult patients diagnosed <1 year prior to enrolment with idiopathic, familial or anorexigen-induced PAH. The FPHN cohort comprised 1737 patients with group 1 PAH. Application of FPHN parameters to REVEAL and REVEAL risk scores to FPHN demonstrated estimated hazard ratios that were consistent between studies and had high probabilities of concordance (hazard ratios of 0.72, 95% CI 0.64-0.80, and 0.73, 95% CI 0.70-0.77, respectively). The REVEAL risk score calculator and FPHN ItinérAIR-HTAP predictive equation showed good discrimination and calibration for prediction of survival in the FPHN and REVEAL cohorts, respectively, suggesting prognostic generalisability in geographically different PAH populations. Once prospectively validated, these may become valuable tools in clinical practice.

Deletion of the Correia element in the mtr gene complex of Neisseria meningitidis.

The mtr gene complex in Neisseria meningitidis encodes an efflux pump that is responsible for export of antibacterial hydrophobic agents. The promoter region of the mtrCDE operon harbours an insertion sequence known as a Correia element, and a binding site for the integration host factor (IHF) is present at the centre of the Correia element. It has been suggested that the expression of the mtrCDE operon in meningococci is subject to transcriptional regulation by the IHF and post-transcriptional regulation by cleavage in the inverted repeat of the Correia element. The promoter region of the mtrCDE operon as well as the association of changes at that point with decreased susceptibility to antimicrobial drugs in 606 Neisseria meningitidis strains were analysed in this study. Two different deletions were present in the analysed region. The first one, found in seven strains, corresponded to absence of the Correia element. The second one, affecting the -10 region and first 100 bp of the mtrR gene and present in 57 isolates, was only found in ST-1624 isolates. None of the deletions were associated with decreased susceptibility to antimicrobial drugs. Although most of the meningococcal strains carry the Correia element at that position, its deletion is not an exception.

Molecular characterization of invasive serogroup Y Neisseria meningitidis strains isolated in the Latin America region.

OBJECTIVES: To improve the understanding of serogroup Y invasive meningococcal disease (IMD) in Latin America, particularly IMD molecular epidemiology; 166 Y serogroup isolates received at the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, and Costa Rica during 2000-2006 were characterized by their molecular markers. METHODS: This analysis included serological assays to determine serogroup/serotype/serosubtype, DNA sequencing and genotyping of the porB and/or porA genes, multilocus sequence typing (MLST) and fetA allele determination. RESULTS: Sixteen different antigenic combinations were observed. Sixty-two (37.3%) isolates were NT:P1.5 and 36 (21.7%) isolates were 14:NST. Thirty-two different STs appeared, but 3 STs (ST-1624, ST-23, and ST-5770) accounted for 69.9% (116) of the strains. Most of the IMD isolates belonged to the ST-23, ST-167 clonal complexes or the group composed by ST-5770 and related STs. CONCLUSIONS: Isolates obtained in Colombia and Costa Rica were similar to that of the United States, in that most sequence types belonged to the ST-23 clonal complex. IMD isolates found in Argentina appear to be the result of an independent event and did not spread from nearby countries, being the sequence type ST-1624 (ST-167 clonal complex) the most frequently found. We were unable to correlate an antigenic shift of outer membrane proteins with an increase of serogroup Y meningococcal cases in our collection of isolates.

Meningitis epidemics in Africa: a brief overview.

Every year, meningococcal meningitis causes thousands of deaths within the meningitis belt in sub-Saharan African countries. Large epidemic waves occur with a periodicity of 5-12 years. The waves do correspond to molecular changes in the expression of capsular or subcapsular antigens, which allow the bug to spread in susceptible populations. Serogroup A remains the major killer, even if in 2002, serogroup W135 ST-11 emerged in Burkina Faso, causing an important epidemic. However, the surveillance in the following years has showed a decrease in the W135 incidence and a clear predominance of serogroup A. Moreover, a new serogroup A strain belonging to ST-2859 seems to emerge and does represent a new threat for the coming seasons. In a vaccine perspective, and especially in the context of the development of an A conjugate vaccine; it is the key to strengthen the surveillance systems and to include molecular epidemiology as a tool for monitoring the molecular evolution of Neisseria meningitidis in Africa.