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Seasonal influenza vaccination rates remain low, and contribute to preventable influenza cases, hospitalizations, and deaths in the US. While numerous interventions have been implemented to increase vaccine uptake, there is a need to determine which interventions contribute most to vaccine willingness, particularly among age groups with vaccination rates that have plateaued at suboptimal levels. This study aimed to quantify the relative effect of multiple interventions on vaccine willingness to receive influenza vaccine in three age groups using a series of hypothetical situations with different behavioral interventions. We assessed the relative impact of four categories of interventions: source of vaccine messages, type of vaccination messages, vaccination incentives, and ease of vaccine access using a discrete choice experiment. Within each category, we investigated the role of four different attributes to measure their relative contribution to willingness to be vaccinated by removing one option from each of the intervention categories. Among the 1,763 Minnesota residents who volunteered for our study, participants expressed vaccine willingness in over 80% of the scenarios presented. Easy access to drop-in vaccination sites had the greatest impact on vaccine willingness in all age groups. Among the younger age group, small financial incentives also contributed to high vaccine willingness. Our results suggest that public health programs and vaccination campaigns may improve their chances of successfully increasing vaccine willingness if they offer interventions preferred by adults, including facilitating convenient access to vaccination and offering small monetary incentives, particularly for young adults.

Background The start of the COVID-19 vaccination campaign among French healthcare and welfare sector workers in January 2021 offered an opportunity to study psychological antecedents of vaccination in this group. Aim We explored whether knowledge and attitude items related to social conformism and confidence in systems contributed to explaining intention for COVID-19 vaccination. Methods We developed a knowledge and attitude questionnaire with 30 items related to five established and two hypothetical psychological antecedents of vaccination (KA-7C). The online questionnaire was distributed from 18 December 2020 to 1 February 2021 through chain-referral via professional networks, yielding a convenience sample. We used multivariable logistic regression to explore the associations of individual and grouped KA-7C items with COVID-19 vaccine intention. Results Among 5,234 participants, the vaccine intention model fit (pseudo R-squared values) increased slightly but significantly from 0.62 to 0.65 when adding social conformism and confidence in systems items. Intention to vaccinate was associated with the majority opinion among family and friends (OR: 11.57; 95% confidence interval (CI): 4.51–29.67) and a positive perception of employer’s encouragement to get vaccinated (vs negative; OR: 6.41; 95% CI: 3.36–12.22). The strongest association of a knowledge item was identifying the statement ‘Some stages of vaccine development (testing) have been skipped because of the epidemic emergency.’ as false (OR: 2.36; 95% CI: 1.73–3.22). Conclusion The results suggest that social conformism and confidence in systems are distinct antecedents of vaccination among healthcare and welfare workers, which should be taken into account in vaccine promotion.

International audience; Background: We previously conducted a single-profile discrete choice experiment to elicit preferences of adolescents around HPV vaccine communication, finding that only half of participants made variable choices (non-uniform respondents) from which preferences were elicited. In this paper we provide a framework to evaluate post-choice certainty information to elicit preferences even among respondents who uniformly accepted (serial demanders) or refused (serial non-demanders) hypothetical vaccination scenarios.Methods: During an in-class online questionnaire among 1458 French adolescents aged 13-15 years old, we collected certainty levels (0-10) after decisions on nine hypothetical scenarios, including four vaccination attributes: information on vaccine-preventable disease type, on vaccine safety, on potential for indirect protection and on vaccine coverage. We developed a vaccine eagerness scale (ranging from -10 to 10), by combining information on the binary decision (accept vs. refuse the hypothetical vaccine) and the decision certainty level. We used random effects linear regressions to evaluate attributes' impact on vaccine eagerness. Sensitivity analyses were performed taking into account low response quality, assessed as invariant certainty and low response time.Results: Attributes' impact on decision certainty were similar between serial demanders (N = 659) and non-uniform respondents (N = 711): mentioning a positive benefit-risk balance significantly decreased certainty to accept (coefficient -0.93), while information on 80% coverage in other countries (+0.33) and potential for disease elimination (+0.09) increased it. Among serial non-demanders, significant attribute impacts were observed only after exclusion of low-quality responses (N = 31): a potential for disease elimination (coefficient: +0.24) and 80% coverage in other countries (+0.42) significantly increased certainty of refusing vaccination. Combining decision and certainty into a vaccine eagerness indicator allowed analysing preferences in the full sample, including "hesitant" respondents, who were sensitive to the content of the vaccination profile.Conclusion: Choice certainty informs on respondents' preferences in single-profile discrete-choice experiments, in particular among those with uniform responses.

ObjectivesTo analyse preferences around promotion of COVID-19 vaccination among workers in the healthcare and welfare sector in Fance at the start of the vaccination campaign.DesignSingle-profile discrete-choice experiment. Respondents in three random blocks chose between accepting or rejecting eight hypothetical COVID-19 vaccination scenarios.Setting4346 healthcare and welfare sector workers in France, recruited through nation-wide snowball sampling, December 2020 to January 2021.OutcomeThe primary outcomes were the effects of attributes’ levels on hypothetical acceptance, expressed as ORs relative to the reference level. The secondary outcome was vaccine eagerness as certainty of decision, ranging from −10 to +10.ResultsAmong all participants, 61.1% made uniform decisions, including 17.2% always refusing vaccination across all scenarios (serial non-demanders). Among 1691 respondents making variable decisions, a strong negative impact on acceptance was observed with 50% vaccine efficacy (compared with 90% efficacy: OR 0.05, 95% CI 0.04 to 0.06) and the mention of a positive benefit–risk balance (compared with absence of severe and frequent side effects: OR 0.40, 0.34 to 0.46). The highest positive impact was the prospect of safely meeting older people and contributing to epidemic control (compared with no indirect protection: OR 4.10, 3.49 to 4.82 and 2.87, 2.34 to 3.50, respectively). Predicted acceptance was 93.8% for optimised communication on messenger RNA vaccines and 16.0% for vector-based vaccines recommended to ≥55-year-old persons. Vaccine eagerness among serial non-demanders slightly but significantly increased with the prospect of safely meeting older people and epidemic control and reduced with lower vaccine efficacy.DiscussionVaccine promotion towards healthcare and welfare sector workers who hesitate or refuse vaccination should avoid the notion of benefit–risk balance, while collective benefit communication with personal utility can lever acceptance. Vaccines with limited efficacy will unlikely achieve high uptake.

International audience; Background: Human Papillomavirus (HPV) vaccine coverage in France is below 30%, despite proven effectiveness against HPV infections and (pre-)cancerous cervical lesions. To optimise vaccine promotion among adolescents, we used a discrete choice experiment (DCE) to identify optimal statements regarding a vaccination programme, including vaccine characteristics.Methods: Girls and boys enrolled in the last two years of five middle schools in three French regions (aged 13-15 years) participated in an in-class cross-sectional self-administered internet-based study. In ten hypothetical scenarios, participants decided for or against signing up for a school-based vaccination campaign against an unnamed disease. Scenarios included different levels of four attributes: the type of vaccine-preventable disease, communication on vaccine safety, potential for indirect protection, and information on vaccine uptake among peers. One scenario was repeated with an added mention of sexual transmission.Results: The 1,458 participating adolescents (estimated response rate: 89.4%) theoretically accepted vaccination in 80.1% of scenarios. All attributes significantly impacted theoretical vaccine acceptance. Compared to a febrile respiratory disease, protection against cancer was motivating (odds ratio (OR) 1.29 [95%-CI 1.09-1.52]), but not against genital warts (OR 0.91 [0.78-1.06]). Compared to risk negation ("vaccine does not provoke serious side effects"), a reference to a positive benefit-risk balance despite a confirmed side effect was strongly dissuasive (OR 0.30 [0.24-0.36]), while reference to ongoing international pharmacovigilance without any scientifically confirmed effect was not significantly dissuasive (OR 0.86 [0.71-1.04]). The potential for indirect protection motivated acceptance among girls but not boys (potential for eliminating the disease compared to no indirect protection, OR 1.57 [1.25-1.96]). Compared to mentioning "insufficient coverage", reporting that ">80% of young people in other countries got vaccinated" motivated vaccine acceptance (OR 1.94 [1.61-2.35]). The notion of sexual transmission did not influence acceptance.Conclusion: HPV vaccine communication to adolescents can be tailored to optimise the impact of promotion efforts.

International audience; In this stated preferences study, we describe for the first time French citizens’ preferences for various epidemic control measures, to inform longer-term strategies and future epidemics. We used a discrete choice experiment in a representative sample of 908 adults in November 2020 (before vaccination was available) to quantify the trade-off they were willing to make between restrictions on the social, cultural, and economic life, school closing, targeted lockdown of high-incidence areas, constraints to directly protect vulnerable persons (e.g., self-isolation), and measures to overcome the risk of hospital overload. The estimation of mixed logit models with correlated random effects shows that some trade-offs exist to avoid overload of hospitals and intensive care units, at the expense of stricter control measures with the potential to reduce individuals’ welfare. The willingness to accept restrictions was shared to a large extent across subgroups according to age, gender, education, vulnerability to the COVID-19 epidemic, and other socio-demographic or economic variables. However, individuals who felt at greater risk from COVID-19, and individuals expressing high confidence in the governmental management of the health and economic crisis, more easily accepted all these restrictions. Finally, we compared the welfare impact of alternative strategies combining different epidemic control measures. Our results suggest that policies close to a targeted lockdown or with medically prescribed self-isolation were those satisfying the largest share of the population and achieving high gain in average welfare, while average welfare was maximized by the combination of all highly restrictive measures. This illustrates the difficulty in making preference-based decisions on restrictions.

Background The Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, to what extent PMVCs are associated with a decreased risk of outbreak has not yet been quantified. Methods and findings We used the self-controlled case series (SCCS) method to assess the association between the occurrence of yellow fever outbreaks and the implementation of PMVCs at the province level in the African endemic region. As all time-invariant confounders are implicitly controlled for in the SCCS method, this method is an alternative to classical cohort or case–control study designs when the risk of residual confounding is high, in particular confounding by indication. The locations and dates of outbreaks were identified from international epidemiological records, and information on PMVCs was provided by coordinators of vaccination activities and international funders. The study sample consisted of provinces that were both affected by an outbreak and targeted for a PMVC between 2005 and 2018. We compared the incidence of outbreaks before and after the implementation of a PMVC. The sensitivity of our estimates to a range of assumptions was explored, and the results of the SCCS method were compared to those obtained through a retrospective cohort study design. We further derived the number of yellow fever outbreaks that have been prevented by PMVCs. The study sample consisted of 33 provinces from 11 African countries. Among these, the first outbreak occurred during the pre-PMVC period in 26 (79%) provinces, and during the post-PMVC period in 7 (21%) provinces. At the province level, the post-PMVC period was associated with an 86% reduction (95% CI 66% to 94%, p < 0.001) in the risk of outbreak as compared to the pre-PMVC period. This negative association between exposure to PMVCs and outbreak was robustly observed across a range of sensitivity analyses, especially when using quantitative estimates of vaccination coverage as an alternative exposure measure, or when varying the observation period. In contrast, the results of the cohort-style analyses were highly sensitive to the choice of covariates included in the model. Based on the SCCS results, we estimated that PMVCs were associated with a 34% (95% CI 22% to 45%) reduction in the number of outbreaks in Africa from 2005 to 2018. A limitation of our study is the fact that it does not account for potential time-varying confounders, such as changing environmental drivers of yellow fever and possibly improved disease surveillance. Conclusions In this study, we provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. This study illustrates that the SCCS method can be advantageously applied at the population level in order to evaluate a public health intervention., In this cohort study, Kévin Jean and colleagues correlate lower risk of disease outbreaks with mass vaccination against yellow fever., Author summary Why was this study done? Yellow fever is a mosquito-borne, vaccine-preventable disease that may cause large urban outbreaks, especially in tropical African regions. Since 2006, preventive mass vaccination campaigns (PMVCs) have been implemented in many African provinces. These are large-scale vaccination campaigns targeting all or most age groups in a specific area. The preventive impact PMVCs may have on the risk of yellow fever outbreak has not been quantified yet. What did the researchers do and find? We used the self-controlled case series (SCCS) method to assess the association between PMVCs and outbreak risk at the province level in 34 African countries between 2005 and 2018. We compared pre- and post-PMVC periods within each province individually, thus implicitly controlling for all possible confounders that do not vary in time, especially the fact that provinces indicated for PMVCs are generally those considered at highest baseline risk of yellow fever (confounding by indication). At the province level, we estimated that implementation of PMVCs was associated with an 86% reduction (95% CI 66% to 94%) in the risk of yellow fever outbreak. A complete cohort analysis provided less reliable results than the SCCS method, likely because of confounding by indication that was not entirely controlled for by adjusting for known drivers of yellow fever. We further estimated that all PMVCs conducted between 2006 and 2018 in Africa may have reduced the total number of yellow fever outbreaks by 34% (95% CI 22% to 45%). What do these findings mean? These results provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. These results may encourage rapid rescheduling of yellow fever PMVCs that have been postponed due to the COVID-19 pandemic. The SCCS design may be advantageously applied at the population level to assess the impact of public health interventions.

Background: Healthcare workers (HCWs) are prioritised for COVID-19 vaccination, but coverage is staggering in France below 70%. Analysing their vaccination preferences is crucial to understand suboptimal uptake and identify levers to increase acceptance among those hesitating. Methods: : We conducted an online single-profile discrete choice experiment (DCE) among a snowballing sample of French HCWs, recruited during December 2020 to January 2021. Respondents in three random blocks chose between accepting or rejecting eight hypothetical COVID-19 vaccination scenarios. The effects of attributes’ levels on hypothetical acceptance were evaluated using mixed logit models, and on vaccine eagerness (certainty of decision, from -10 to +10) using linear random effect models. Results: Among 4346 participants, 61.1% made uniform decisions, including 17.2% always refusing vaccination across all scenarios (serial non-demanders). Among 1691 respondents making variable decisions, a strong negative impact on acceptance was observed with 50% vaccine efficacy (compared to 90% efficacy: odds ratio 0.05, 95%-CI 0.04-0.06), and the mention of a positive benefit-risk balance (compared to absence of severe and frequent side effects: OR 0.40, 0.34-0.46. The highest positive impact was the prospect of safely meeting older people and contributing to epidemic control (compared to no indirect protection: OR 4.10, 3.49-4.82 and 2.87, 2.34-3.50, respectively. Predicted acceptance was 93.8% for optimized communication on mRNA vaccines and 16.0% for vector-based vaccines recommended to ≥55-year-old persons. Vaccine eagerness among serial non-demanders slightly but significantly increased with the prospect of safely meeting older people and epidemic control; and reduced with lower vaccine efficacy. Discussion: Vaccine promotion towards HCWs who hesitate or refuse vaccination, should avoid the notion of benefit-risk balance, while collective benefit communication with personal utility can lever acceptance. Vaccines with limited efficacy will unlikely achieve high uptake.

Introduction The Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, by how much PMVCs are associated with a decreased risk of outbreak to occur has not yet been quantified. Methods and Findings We used the self-controlled case series (SCCS) method to assess the association between the occurrence of yellow fever outbreaks and the implementation of PMVCs at the province level in the African endemic region. As all time-invariant confounders are implicitly controlled for, the SCCS method is an alternative to classical cohort or case-control study designs when the risk of residual confounding is high, in particular confounding by indication. The location and dates of outbreaks were identified from international epidemiological records, and information on PMVCs was provided by coordinators of vaccination activities and international funders. The study sample consisted of provinces that were both affected by an outbreak and targeted for a PMVC between 2005 and 2018. We compared the relative incidence of outbreaks before and after the implementation of a PMVC. The sensitivity of our estimates to a range of assumptions was explored, and the results of the SCCS method were compared to those obtained through a retrospective cohort study design. We further derived the number of yellow fever outbreaks that have been prevented by PMVCs. The study sample consisted of 33 provinces from 11 African countries. Among these, outbreaks occurred during the pre-PMVC period in 26 (79%) provinces versus 7 (21%) occurring in the post-PMVC period. At the province level, the post-PMVC period was associated with a 86% reduction (95% Confidence interval 66% to 94%, p-value A limitation of our study is the fact that it does not account for potential time-varying confounders, such as changing environmental drivers of yellow fever or possibly improved disease surveillance. Conclusion In this study, we provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. This study illustrates that the SCCS method can be advantageously applied at the population level in order to evaluate a public health intervention. AUTHOR SUMMARY Why Was This Study Done? Yellow fever is a mosquito-borne vaccine-preventable disease that may cause large urban outbreaks, especially in tropical African regions. Since 2006, Preventive Mass Vaccination Campaigns (PMVCs) have been implemented in many African provinces. These are large scale vaccination campaigns targeting all or most age group in a specific area. The preventive impact PMVCs may have on the risk of yellow fever outbreak has not been quantified yet. What Did the Researchers Do and Find? We used the self-controlled case series (SCCS) method to assess the association between PMVCs and outbreak risk at the province level over 34 African countries between 2005 and 2018. Using this method, we compared pre- and post-PMVC period are compared within each province individually, thus controlling for all possible confounders that do not vary in time, especially the fact that provinces indicated for PMVCs are generally those considered at highest baseline risk of yellow fever (ie confounding by indication). At the province level, we estimated that implementation of PMVCs was associated with an 86% reduction (66% to 94%) in the risk of yellow fever outbreak. Results from a complete cohort analysis provided less reliable results than the SCCS method, likely because of confounding by indication that was not entirely controlled for by adjusting on known drivers of yellow fever. We further estimated that all PMVCs conducted between 2006 and 2018 in Africa may have reduced the total number of yellow fever outbreaks by 34% (22% to 45%). What Do These Findings Mean? These results provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. These results may encourage rapid re-scheduling of yellow fever PMVCs that have been postponed due to the COVID-19 pandemic. The SCCS design may be advantageously applied at the population level to assess the impact of public health interventions.

Resume Position du probleme L’objectif de cette etude est de decrire un outil permettant d’estimer en quasi-temps reel la couverture vaccinale contre la grippe saisonniere chez les 65 ans et plus a partir des ventes de vaccins en pharmacie. Methodes Les donnees de ventes de vaccins proviennent d’un echantillon stratifie de 3004 pharmacies en France metropolitaine et sont disponibles le jour suivant les ventes. Les couvertures vaccinales estimees entre 2009 et 2014 ont ete comparees avec celles obtenues a partir des donnees de remboursements aux affilies du Regime general. Resultats Les couvertures vaccinales saisonnieres estimees sont tres correlees a celles obtenues avec les donnees de remboursements. Elles sont aussi legerement superieures, ce qui peut s’expliquer par l’inclusion de vaccins non rembourses et la prise en compte de l’ensemble des 65 ans et plus, tous regimes confondus. Nous avons developpe un outil accessible en ligne permettant d’acceder quotidiennement a une estimation de la couverture vaccinale des 65 ans et plus lors de chaque campagne de vaccination. Conclusion L’outil developpe permet de fournir une information fiable et en quasi-temps reel sur la couverture vaccinale des 65 ans et plus. Il peut etre utilise pour evaluer et ajuster les messages de sante publique.

Background Rotavirus is a major cause of severe gastroenteritis in children worldwide. The disease burden has been substantially reduced in countries where rotavirus vaccines are used. Given the risk of vaccine-induced intussusception, the benefit–risk balance of rotavirus vaccination has been assessed in several countries, however mostly without considering indirect protection effects. Aim We performed a benefit–risk analysis of rotavirus vaccination accounting for indirect protection in France among the 2018 population of children under the age of 5 years. Methods To incorporate indirect protection effects in the benefit formula, we adopted a pseudo-vaccine approach involving mathematical approximation and used a simulation design to provide uncertainty intervals. We derived background incidence distributions from quasi-exhaustive health claim data. We examined different coverage levels and assumptions regarding the waning effects and intussusception case fatality rate. Results With the current vaccination coverage of < 10%, the indirect effectiveness was estimated at 6.4% (+/− 0.4). For each hospitalisation for intussusception, 277.0 (95% uncertainty interval: (165.0–462.1)) hospitalisations for rotavirus gastroenteritis were prevented. Should 90% of infants be vaccinated, indirect effectiveness would reach 57.9% (+/− 3.7) and the benefit–risk ratio would be 192.4 (95% uncertainty interval: 116.4–321.3). At a coverage level of 50%, indirect protection accounted for 27% of the prevented rotavirus gastroenteritis cases. The balance remained in favour of the vaccine even in a scenario with a high assumption for intussusception case fatality. Conclusions These findings contribute to a better assessment of the rotavirus vaccine benefit–risk balance.

Despite improved surveillance capacities and WHO recommendations for subdistrict analysis, routine epidemic surveillance of acute bacterial meningitis in the African meningitis belt remains largely limited to the district level. We evaluated the appropriateness and performance of analyses at higher spatial resolution. We used suspected meningitis surveillance data at health centre (HC) resolution from Burkina Faso from 14 health districts spanning years 2004–2014 and analysed them using spatio-temporal statistics and generative models. An operational analysis compared epidemic signals at district and HC-level using weekly incidence thresholds. Eighty-four percent (N = 98/116) of epidemic clusters spanned only one HC-week. Spatial propagation of epidemic clusters was mostly limited to 10–30 km. During the 2004–2009 (with serogroup A meningitis) and 2010–2014 (after serogroup A elimination) period, using weekly HC-level incidence thresholds of 100 and 50 per 100,000 respectively, we found a gain in epidemic detection and timeliness in 9 (41% of total) and 10 (67%), respectively, district years with at least one HC signal. Individual meningitis epidemics expanded little in space, suggesting that a health centre level analysis is most appropriate for epidemic surveillance. Epidemic surveillance could gain in precision and timeliness by higher spatial resolution. The optimal threshold should be defined depending on the current background incidence of bacterial meningitis.

International audience; In this article of EBioMedicine, Topaz and colleagues [1] present a phylogenetic overview with more than 700 meningococcal strains isolated since the introduction of a serogroup A-specific conjugate vaccine (MenAfriVac®) in the meningitis belt. This vaccination has led to quasi-elimination of serogroup A disease, which used to be the predominant burden, but the emergence of a new serogroup C strain during the vaccination roll-out substantially reduced the net benefit for the region.

International audience; A conjugate vaccine for Neisseria meningitidis serogroup A (MenAfriVac) was introduced through mass campaigns in people aged 1–29 years in the African meningitis belt and is now being added to national infant immunisation programmes. 1 Following the mass campaigns in 2010–17, incidence of N meningitidis serogroup A meningitis has declined from a hyperendemic pattern with regular epidemics to a few sporadic cases. 2 The hope is that control of the disease will be long lasting. The mechanism for such control would be the initial interruption of circulation of N meningitidis serogroup A in the population through the effect of the vaccine against asymptomatic nasopharyngeal infection, followed by sustained direct protection against disease, including in new birth cohorts. The duration of persistence of antibodies is a major variable in this scheme.

International audience; OBJECTIVE: To inform public health recommendations, we evaluated the effectiveness and efficiency of current and hypothetical surveillance and vaccine response strategies against Neisseria meningitidis C meningitis epidemics in 2015 in Niger.METHODS : We analysed reports of suspected and confirmed cases of meningitis from the region of Dosso during 2014 and 2015. Based on a definition of epidemic signals, the effectiveness and efficiency of surveillance and vaccine response strategies were evaluated by calculating the number of potentially vaccine-preventable cases and number of vaccine doses needed per epidemic signal.RESULTS : A total of 4763 weekly health area reports, collected in 90 health areas with 1282 suspected meningitis cases, were included. At a threshold of 10 per 100 000, the total number of estimated vaccine-preventable cases was 29 with district-level surveillance and vaccine response, 141 with health area-level surveillance and vaccination and 339 with health area-level surveillance and district-level vaccination. While being most effective, the latter strategy required the largest number of vaccine doses (1.8 million), similar to the strategy of surveillance and vaccination at district level (1.3 million), whereas the strategy of surveillance and vaccination at health area level would have required only 0.8 million doses. Thus, efficiency was lowest for district-level surveillance and highest for health area-level surveillance with district-level vaccination.CONCLUSION : In this analysis, we found that effectiveness and efficiency were higher at health area-level surveillance and district-level vaccination than for other strategies. Use of N. meningitidis C vaccines in a preventive strategy thus should be considered, in particular as most reactive vaccine response strategies in our analysis had little impact on disease burden.

International audience; Background: In Burkina Faso, serogroup A meningococcal (NmA) conjugate vaccine (PsA-TT, MenAfriVac) was introduced through a mass campaign in children and adults in December 2010. Similar to a serological survey in 2011, we followed population-level antibody persistence for 5 years after the campaign and estimated time of return to previously-published pre-vaccination levels.Methods: We conducted 2 cross-sectional surveys in 2013 and early 2016, including representative samples (N = 600) of the general population of Bobo-Dioulasso, Burkina Faso. Serum bactericidal antibody titers (rabbit complement) were measured against NmA reference strain F8236 (SBA-ref), NmA strain 3125 (SBA-3125), and NmA-specific immunoglobulin G (IgG) concentrations.Results: During the 2016 survey, in different age groups between 6 and 29 years, the relative changes in geometric means compared to 2011 values were greater among younger age groups. They were between -87% and -43% for SBA-ref; -99% and -78% for SBA-3125; and -89% and -63% for IgG. In linear extrapolation of age-specific geometric means from 2013 to 2016, among children aged 1-4 years at the time of the PsA-TT campaign, a return to pre-vaccination levels should be expected after 12, 8, and 6 years, respectively, according to SBA-ref, SBA-3125, and IgG. Among older individuals, complete return to baseline is expected at the earliest after 11 years (SBA-ref and SBA-3125) or 9 years (IgG).Conclusions: Based on SBA-3125, a booster campaign after 8 years would be required to sustain direct immune protection for children aged 1-4 years during the PsA-TT campaign. Antibodies persisted longer in older age groups.

The pathophysiological mechanisms underlying the seasonal dynamic and epidemic occurrence of bacterial meningitis in the African meningitis belt remain unknown. Regular seasonality (seasonal hyperendemicity) is observed for both meningococcal and pneumococcal meningitis and understanding this is critical for better prevention and modelling. The two principal hypotheses for hyperendemicity during the dry season imply (1) an increased risk of invasive disease given asymptomatic carriage of meningococci and pneumococci; or (2) an increased transmission of these bacteria from carriers and ill individuals. In this study, we formulated three compartmental deterministic models of seasonal hyperendemicity, featuring one (model1-‘inv’ or model2-‘transm’), or a combination (model3-‘inv-transm’) of the two hypotheses. We parameterised the models based on current knowledge on meningococcal and pneumococcal biology and pathophysiology. We compared the three models' performance in reproducing weekly incidences of suspected cases of acute bacterial meningitis reported by health centres in Burkina Faso during 2004–2010, through the meningitis surveillance system. The three models performed well (coefficient of determination R2, 0.72, 0.86 and 0.87, respectively). Model2-‘transm’ and model3-‘inv-transm’ better captured the amplitude of the seasonal incidence. However, model2-‘transm’ required a higher constant invasion rate for a similar average baseline transmission rate. The results suggest that a combination of seasonal changes of the risk of invasive disease and carriage transmission is involved in the hyperendemic seasonality of bacterial meningitis in the African meningitis belt. Consequently, both interventions reducing the risk of nasopharyngeal invasion and the bacteria transmission, especially during the dry season are believed to be needed to limit the recurrent seasonality of bacterial meningitis in the meningitis belt.

8 pages; International audience; Background : Bacterial meningitis causes a high burden of disease in the African meningitis belt, with regular seasonal hyperendemicity and sporadic short, but intense, localized epidemics during the late dry season occurring at a small spatial scale [i.e., below the district level, in individual health centers (HCs)]. In addition, epidemic waves with larger geographic extent occur every 7–10 y. Although atmospheric dust load is thought to be an essential factor for hyperendemicity, its role for localized epidemics remains hypothetic.Objectives : Our goal was to evaluate the association of localized meningitis epidemics in HC catchment areas with the dust load and the occurrence of cases in the same population early in the dry season.Methods : We compiled weekly reported cases of suspected bacterial meningitis at the HC resolution for 14 districts of Burkina Faso for the period 2004–2014. Using logistic regression, we evaluated the association of epidemic HC-weeks with atmospheric dust [approximated by the aerosol optical thickness (AOT) satellite product] and with the observation of early meningitis cases during October–December.Results : Although AOT was strongly associated with epidemic HC-weeks in crude analyses across all HC-weeks during the meningitis season [odds ratio (OR) = 6.82; 95% CI: 4.90, 9.50], the association was no longer apparent when controlling for calendar week (OR = 0.92; 95% CI: 0.60, 1.50). The number of early meningitis cases reported during October–December was associated with epidemic HC-weeks in the same HC catchment area during January–May of the following year (OR for each additional early case =1.14 ; 95% CI: 1.06, 1.21).Conclusions : Spatial variations of atmospheric dust load do not seem to be a factor in the occurrence of localized meningitis epidemics, and the factor triggering them remains to be identified. The pathophysiological mechanism linking early cases to localized epidemics is not understood, but their occurrence and number of early cases could be an indicator for epidemic risk.

Background Capsular group X N. meningitidis (MenX) has emerged as a cause of localized disease outbreaks in sub-Saharan Africa, but the human immune response following exposure to MenX antigens is poorly described. We therefore assessed the natural immunity against MenX in individuals who were living in an area affected by a MenX outbreak during 2007 in Togo, West Africa. During 2009, 300 healthy individuals (100 aged 3–5 years, 100 aged 13–19 years and 100 aged 20–25 years) were included in the study, and serum responses were compared with sera from age-matched controls from the U.K. and Burkina Faso. Methods MenX serum bactericidal antibody (SBA) was measured using rabbit complement, and antibodies against MenX polysaccharide (XPS) and outer membrane vesicles (XOMVs) were quantified by ELISA. Results The proportion of Togolese individuals with an SBA titer of ≥8 against the MenX strain was 29% (95% confidence interval (CI) 18–41) among those aged 3–5 years, 34% (95% CI 9–60) among those aged 13–19 years and 32% (95% CI 24–40) among those aged 20–25 years. These were significantly higher than observed in the control populations from the U.K (range 13–16%) and Burkina Faso (range 2–6%). Conclusion In Togolese individuals, the concentration of serum IgG against XPS was higher among the two older age groups as compared to the youngest age group. Antibody concentrations against MenX PS correlated significantly with SBA titers. This supports further development of a MenX PS based conjugate vaccine. Further studies are needed to verify the ability of MenX PS to induce SBA in humans.

Background Several concepts are available to explain vaccine decision making by individual and inter-individual factors, including risk perception, social conformism and altruism. However, only a few studies have quantified the weight of these determinants in vaccine acceptance. Using a conjoint analysis tool, we aimed at eliciting preferences in a student population regarding vaccination against a rare, severe and rapidly evolving hypothetical disease, similar to meningococcal serogroup C meningitis or measles. Methods During March-May 2016, we conducted an emailing survey among university students aged 18–24 years (N = 775) in Rennes, France. Participants were asked to decide for or against immediate vaccination in 24 hypothetical scenarios, containing various levels of four attributes: epidemic situation, adverse events, information on vaccination coverage, and potential for indirect protection. Data were analysed using random effect estimator logit models. Results Participants accepted on average 52% of scenarios and all attributes significantly impacted vaccination acceptance. The highest positive effects were seen with an epidemic situation (OR 3.81, 95%-CI 3.46–4.19), 90% coverage in the community (3.64, 3.15–4.20) and potential for disease elimination from the community (2.87, 2.53–3.26). Information on “insufficient coverage” was dissuasive (vs. none of friends vaccinated: 0.65, 0.56–0.75). Controversy had a significantly greater negative effect than a confirmed risk of severe adverse events (OR 0.05 vs. 0.22). In models including participant characteristics, preference weights were unchanged, while trust in health authorities and vaccination perceptions strongly influenced acceptance themselves. The greatest significant variation of preference weights between subgroups was observed with controversy among students using alternative medicine daily (OR 0.28) and among students relying on scientific vaccine information (OR 0.02). Conclusions Among young adults, potential for indirect protection and factual information on coverage in the community and potential side effects positively impact theoretical vaccine acceptance. Conjoint analyses should be conducted to understand vaccine hesitancy in specific vaccination programs.

Meningococcal meningitis epidemics in the African meningitis belt consist of localised meningitis epidemics (LME) that reach attack proportions of 1% within a few weeks. A meningococcal serogroup A conjugate vaccine was introduced in meningitis belt countries from 2010 on, but LME due to other serogroups continue to occur. The mechanisms underlying LME are poorly understood, but an association with respiratory pathogens has been hypothesised. We analysed national routine surveillance data in high spatial resolution (health centre level) from 13 districts in Burkina Faso, 2004–2014. We defined LME as a weekly incidence rate of suspected meningitis ≥75 per 100,000 during ≥2 weeks; and high incidence episodes of respiratory tract infections (RTI) as the 5th quintile of monthly incidences. We included 10,334 health centre month observations during the meningitis season (January-May), including 85 with LME, and 1891 (1820) high-incidence episodes of upper (lower) RTI. In mixed effects logistic regression accounting for spatial structure, and controlling for dust conditions, relative air humidity and month, the occurrence of LME was strongly associated with high incidence episodes of upper (odds ratio 23.9, 95%-confidence interval 3.1–185.3), but not lower RTI. In the African meningitis belt, meningitis epidemics may be triggered by outbreaks of upper RTI.

The epidemiology of bacterial meningitis will change with introduction of meningococcal and pneumococcal conjugate vaccines in the African meningitis belt. The principal objectives of surveillance are to evaluate the impact of vaccination, to detect and investigate epidemics and provide material for research. The capacity of existing surveillance activities in the meningitis belt to meet these objectives varies due to infrastructural and financial constraints. Impact assessment of conjugate vaccine against meningococcal serogroup A will be limited to comparing incidence trends from a few surveillance sites with data obtained before vaccine introduction and to comparing trends in the incidence of suspected cases or localised epidemics in most other settings. The timeliness of detection of epidemics and identification of epidemic meningococcal serogroups could be improved in most countries by analysing suspected case data in health centre level resolution and by investigating outbreaks with mobile teams. For research and impact assessment of pneumococcal conjugate vaccines, several surveillance sites covering at least 0.5 million inhabitants should be maintained which undertake exhaustive case finding and systematic laboratory confirmation of meningitis and pneumonia. Molecular diagnostics will facilitate surveillance in remote areas, but the available techniques should be evaluated for diagnostic performance in the field and long-term sustainability.

Background: Centre MURAZ of Bobo-Dioulasso (Burkina Faso) organized in 2009 and 2010 a system of Cerobro-Spinal Fluid (CSF) collection in eight pilot Districts as an initial step for the future Ministry of Health’s led strategy of individual surveillance in a context of meningococcal conjugate A vaccine introduction. Methods: CSF samples were analyzed with Polymerase Chain Reaction (PCR). This allowed for meningitis etiologies dynamics studies in the pilot Districts. Results: Because of geographical difficulties and lack of means, less than 40% of suspected cases had their CSF analyzed at PCR reference laboratory. In 2009, among confirmed cases at reference laboratory, Sp (Streptococcus pneumonia), NmA (Neisseria meningitis A) and Hib (Hemophilus influenzae b) were responsible respectively for 90%, 6.6% and 4.4% of cases. In 2010, serogroup distribution among confirmed cases was: Sp 62.7%, NmX 32.2% and NmA 5.1%. Sp which was continuously present in Burkina Faso takes more significant proportions, just as serogroup X which until there was sporadically encountered. The attack rates of NmX were tree to twelve times higher than for NmA in the two Districts where NmX has been notified. Conclusion: As a consequence of such results, efforts must be maintained in epidemiologic surveillance field and in reinforcement of laboratory capacities. Fast care should be guaranteed to patients with adequate antibiotics according to country national guideline and chemoprophylaxis measures should be undertaken among contacts of patients to prevent secondary cases. A plea must be made on one hand for pneumococcal vaccine introduction in Burkina Faso and on other hand towards manufacturers for taking into account serogroup X into meningococcal polyvalent vaccine composition. With this polyvalent vaccine including serougruop X, we suggested to conduct periodically mass campaign vaccination of people before the beginning of meningitis epidemiological season.

This study compares the presence of environmental poliovirus in two Argentinean populations using oral poliovirus vaccine (OPV) or inactivated poliovirus vaccine (IPV). From January 2003 to December 2005, Córdoba City used IPV in routine infant immunizations, with the exception of intermittent OPV use in August 2005. Between May 2005 and April 2006, we collected weekly wastewater samples in Córdoba City and the province's three major towns, which continued OPV use at all times. Wastewater samples were processed and analyzed for the presence of poliovirus according to WHO guidelines. During the months of IPV use in Córdoba City, the overall proportion of poliovirus-positive samples was 19%. During an intermittent switch from IPV to OPV, this proportion increased to 100% within 2 months. During the 3 months when IPV was reintroduced to replace OPV, a substantial proportion of samples (25%) remained positive for poliovirus. In the OPV-using sites, on average, 54% of samples were poliovirus positive. Seventy-seven percent of poliovirus isolates showed at least one mutation in the VP1-encoding sequence; the maximum genetic divergence from the Sabin strain was 0.7%. Several isolates showed mutations on attenuation markers in the VP1-encoding sequence. The frequency or type of virus mutation did not differ between periods of IPV and OPV use or by virus serotypes. This study indicates that the sustained transmission of OPV viruses was limited during IPV use in a middle-income country with a temperate climate. The continued importation of poliovirus and genetic instability of vaccine strains even in the absence of sustained circulation suggest that high poliovirus vaccine coverage has to be maintained for all countries until the risk of reintroduction of either wild or vaccine-derived poliovirus is close to zero worldwide.

Streptococcus pneumoniae causes a substantial proportion of meningitis cases in the African meningitis belt; however, few reports exist to quantify its burden and characteristics. We conducted population-based and sentinel hospital surveillance of acute bacterial meningitis among persons of all ages in Burkina Faso and Togo in 2002-2006. S. pneumoniae and other organisms were identified by culture, polymerase chain reaction, or detection of antigen in cerebrospinal fluid (CSF). Information was collected on 2843 patients with suspected acute bacterial meningitis. CSF specimens were collected from 2689 (95%) of the patients; of these 2689, 463 (17%) had S. pneumoniae identified, 234 (9%) had Haemophilus influenzae type b identified, and 400 (15%) had Neisseria meningitidis identified. Of the 463 cases of S. pneumoniae meningitis, 99 (21%) were aged1 year, 71 (15%) were aged 1-4 years, 95 (21%) were aged 5-14 years, and 189 (41%) were agedor=15 years (age was unknown for 9 [2%]). In Burkina Faso, the annual incidence rate of pneumococcal meningitis was 14 cases per 100,000 persons, with annual incidence rates of 77, 33, 10, and 11 cases per 100,000 persons aged1 year,5 years, 5-14 years, andor=15 years, respectively. The case-fatality ratio for S. pneumoniae meningitis was 47% (range for age groups, 44%-52%), and 53% of deaths occurred among those aged5 years. S. pneumoniae meningitis had an epidemic pattern similar to that of N. meningitidis meningitis. Of 48 isolates tested for serotype, 18 were from children aged5 years; of these 18, 3 isolates (17%) each were serotypes 1, 2, and 5, and 5 isolates (28%) were serotype 6A. The 7-, 10-, and 13-valent pneumococcal conjugate vaccines would cover 6%, 39%, and 67% of serotypes identified among children aged5 years, respectively. Of the 30 serotypes identified for patients agedor=5 years, 18 (60%) were serotype 1, whereas no other serotype constituted10%. The 7-, 10-, and 13-valent vaccines would cover 7%, 70%, and 77% of serotypes. Epidemic pneumococcal meningitis in the African meningitis belt countries of Burkina Faso and Togo is common, affects all age groups, and is highly lethal. On the basis of a modest number of isolates from a limited area that includes only meningitis cases, 7-valent pneumococcal conjugate vaccine might have only a limited and short-term role. By contrast, the proposed 10- and 13-valent vaccines would cover most of the identified serotypes. To better inform vaccine policy, continued and expanded surveillance is essential to document serotypes associated with pneumonia, changes in serotype distribution across time, and the impact of vaccine after vaccine introduction.

Few reports documenting the epidemiology of Neisseria meningitidis (Nm) serogroup W135 exist, and none from Togo. During 2003-2005, we conducted acute bacterial meningitis surveillance at three major reference hospitals in Togo. Of 116 Nm identified, 83 (71%) were NmA, 23 (20%) were NmW135, and 10 (9%) did not have a serogroup identified. Nine percent of NmW135 cases and 35% of NmA cases occurred among those aged 15 years or older. The two hospitals in central Togo reported 23% of all Nm cases and 78% of NmW135 cases. Twelve of the 23 NmW135 cases occurred during February-March 2003, while the remaining 11 occurred sporadically over the remaining 18 months of the study. NmW135 meningitis showed pronounced temporal and geographic clustering and occurred almost exclusively among those younger than 15 years old. By the 2004-2005 epidemic season, NmW135 had largely disappeared from Togo for unknown reasons.

A prospective carriage and serological study was conducted in Burkina Faso during the 2003 meningitis season, which was characterized by hyperendemic Neisseria meningitidis serogroup W135 (NmW135) and serogroup A (NmA) disease. Participants were evaluated five times at monthly intervals. In the presence of moderate NmW135 carriage, we found a low prevalence of putatively protective levels of specific immunoglobulin G (IgG) and serum bactericidal antibody (SBA) against NmW135. Specific IgG concentrations and SBA titers against NmA were relatively high in this recently vaccinated population, while no NmA carriage was detected. NmW135 carriage infrequently induced protective immunity against reference or homologous strains, while natural immunity against NmW135 was frequently lost. A vaccine that is effective against W135 will be beneficial for sub-Saharan Africa.

During reinforced surveillance of acute bacterial meningitis in Burkina Faso, meningococcal strains of phenotype NG:NT:NST were isolated from cerebrospinal fluid samples from 3 patients. The strains were negative for the ctrA gene but were positive for the crgA gene. Molecular typing revealed that the strains harbored the capsule null locus (cnl) and belonged to the multilocus sequence type (ST)-192. PorA sequencing showed that all strains were either P1.18-11,42; P1.18,42-1; P1.18-11,42-1; P1.18-11,42-3; or P1.18-12,42-1. Sequencing also showed that all strains were negative for the FetA receptor gene. Serum killing assays showed these strains to be resistant, with the resistance comparable with that of a fully capsular serogroup B strain, MC58. The same strains were found in 14 healthy carriers in the general population of Bobo-Dioulasso (100% of ST-192 isolates tested for cnl). The presence of cnl meningococci that can escape serum killing and cause invasive disease is of concern for future vaccination strategies and should promote rigorous surveillance of cnl meningococcal disease.

International audience; BACKGROUND:A group A meningococcal (MenA) conjugate vaccine, PsA-TT (MenAfriVac), was introduced in Burkina Faso via mass campaigns between September and December 2010, targeting the 1- to 29-year-old population. This study describes specific antibody titers in the general population 11 months later and compares them to preintroduction data obtained during 2008 using the same protocol.METHODS:During October-November 2011, we recruited a representative sample of the population of urban Bobo-Dioulasso aged 6 months to 29 years, who underwent standardized interviews and blood draws. We assessed anti-MenA immunoglobulin G (IgG) concentrations (n = 200) and, using rabbit complement, serum bactericidal antibody (SBA) titers against 2 group A strains: reference strain F8238 (SBAref) (n = 562) and strain 3125 (SBA3125) (n = 200).RESULTS:Among the 562 participants, 481 (86%) were aged ≥23 months and had been eligible for the PsA-TT campaign. Among them, vaccine coverage was 86.3% (95% confidence interval [CI], 82.7%-89.9%). Prevalence of putatively protective antibodies among vaccine-eligible age groups was 97.3% (95% CI, 95.9%-98.7%) for SBAref titers ≥128, 83.6% (95% CI, 77.6%-89.7%) for SBA3125 ≥128, and 84.2% (95% CI, 78.7%-89.7%) for anti-MenA IgG ≥2 µg/mL. Compared to the population aged 23 months to 29 years during 2008, geometric mean titers of SBAref were 7.59-fold higher during 2011, 51.88-fold for SBA3125, and 10.56-fold for IgG.CONCLUSIONS:This study shows high seroprevalence against group A meningococci in Burkina Faso following MenAfriVac introduction. Follow-up surveys will provide evidence on the persistence of population-level immunity and the optimal vaccination strategy for long-term control of MenA meningitis in the African meningitis belt.

Surveillance and epidemic vaccine response would be most effective at the health area level., To inform epidemic response strategies for the African meningitis belt after a meningococcal serogroup A conjugate vaccine was introduced in 2010, we compared the effectiveness and efficiency of meningitis surveillance and vaccine response strategies at district and health area levels using various thresholds of weekly incidence rates. We analyzed reports of suspected cases from 3 regions in Niger during 2002–2012 (154,392 health area weeks), simulating elimination of serogroup A meningitis by excluding health area years with identification of such cases. Effectiveness was highest for health area surveillance and district vaccination (58–366 cases; thresholds 7–20 cases/100,000 doses), whereas efficiency was optimized with health area vaccination (5.6–7.7 cases/100,000 doses). District-level intervention prevented

Streptococcus pneumoniaeserotype 1 (Sp1) constitutes an important cause of seasonal endemic meningitis in all age groups in the African meningitis belt. Despite a higher meningitis incidence, the Burkinabé population has an Sp1-specific antibody seroprevalence similar to that reported in the United Kingdom (UK). We aimed to establish whether the opsonophagocytic activity (OPA) of pneumococcal IgG naturally present in Burkina Faso differs from that seen in individuals in the UK and to compare the OPAs generated by natural and vaccine-induced immunity. Samples collected from pneumococcal vaccine-naive Burkinabé and UK subjects were matched for age (1 to 39 years) and anti-Sp1 IgG level, analyzed for OPA to 3S. pneumoniaeserotypes (1, 5, and 19A), and compared to postvaccine samples. Furthermore, the Burkinabé samples were assessed for IgG avidity and serotype-specific IgM concentrations. One hundred sixty-nine matched serum samples from both populations were selected. A greater proportion of Burkinabé subjects aged 1 to 19 years had functional Sp1 activity (OPA ≥ 8) compared to UK subjects (12% versus 2%,P< 0.001); however, the proportions were similar among adults (9%). The correlation between Sp1 IgG concentration and OPA was good (P< 0.001), but many individuals had nonfunctional IgG, which was not related to avidity. While the Sp1 IgM concentrations correlated with OPA, not all of the function in serum samples with low IgG could be attributed to IgM. Finally, vaccine-induced Sp1-specific IgG was more functional than equivalent amounts of naturally occurring IgG. In conclusion, despite a substantially higher pneumococcal meningitis incidence, no decreased functional immunity to Sp1 could be evidenced in the Burkinabé population compared to that in the population from the UK. Furthermore, the naturally induced antibodies were less functional than vaccine-induced antibodies.

Malawi has extreme poverty and a high-human immunodeficiency virus (HIV) prevalence. Following Haemophilus influenzae type b (Hib) conjugate vaccine introduction during 2002, we evaluated vaccine impact by reviewing hospital surveillance data for acute bacterial meningitis in Blantyre district among children age 1-59 months admitted during 1997-2005. Documented annual Hib meningitis incidence rates decreased from 20-40/100,000 to near zero among both rural and urban residents despite no change in pneumococcal meningitis incidence rates. Before vaccine introduction, an average of 10 children/year had Hib meningitis and HIV infection compared to 2/year during 2003-2004 and none during 2005. Vaccine effectiveness was high following two or more doses of vaccine. The most urgent future need is for a sustainable routine infant immunization program, including a less expensive vaccine that preferably is delivered in a multivalent form.

In the sub-Saharan African meningitis belt there is a region of hyperendemic and epidemic meningitis stretching from Senegal to Ethiopia. The public health approaches to meningitis epidemics, including those related to vaccine use, have assumed that Neisseria meningitidis serogroup A will cause the most disease. During 2001 and 2002, the first large-scale epidemics of serogroup W135 meningitis in sub-Saharan Africa were reported from Burkina Faso. The occurrence of N. meningitidis W135 epidemics has led to a host of new issues, including the need for improved laboratory diagnostics for identifying serogroups during epidemics, an affordable supply of serogroup W135-containing polysaccharide vaccine for epidemic control where needed, and re-evaluating the long-term strategy of developing a monovalent A conjugate vaccine for the region. This review summarizes the existing data on N. meningitidis W135 epidemiology, immunology and vaccines as they relate to meningitis in sub-Saharan Africa.

International audience; BackgroundTo facilitate the interpretation of meningococcal meningitis epidemiology in the “African meningitis belt”, we aimed at obtaining serogroup-specific pooled estimates of incidence, carriage and case-carrier ratios for meningococcal meningitis in the African meningitis belt and describe their variations across the endemic, hyperendemic and epidemic context.MethodsWe conducted a systematic review and meta-analysis of studies reporting serogroup-specific meningococcal meningitis monthly incidence and carriage in the same population and time period. Epidemiological contexts were defined as endemic (wet season, no epidemic), hyperendemic (dry season, no epidemic), and epidemic (dry season, epidemic).FindingsEight studies reporting a total of eighty pairs of serogroup-specific meningococcal meningitis incidence and carriage estimates were included in this review. For serogroup A, changes associated with the transition from endemic to hyperendemic incidence and from hyperendemic to epidemic incidence were 15-fold and 120-fold respectively. Changes in carriage prevalence associated with both transitions were 1-fold and 30-fold respectively. For serogroup W and X, the transition from endemic to hyperendemic incidence involved a 4-fold and 1•1-fold increase respectively. Increases in carriage prevalence for the later transition were 7-fold and 1•7-fold respectively. No data were available for the hyperendemic-epidemic transition for these serogroups. Our findings suggested that the regular seasonal variation in serogroup A meningococcal meningitis incidence between the rainy and the dry season could be mainly driven by seasonal change in the ratio of clinical cases to subclinical infections. In contrast appearance of epidemic incidences is related to a substantial increase in transmission and colonisation and to lesser extent with changes in the case-carrier ratio.ConclusionSeasonal change in the rate of progression to disease given carriage together with variations in frequency of carriage transmission should be considered in models attempting to capture the epidemiology of meningococcal meningitis and mainly to predict meningitis epidemics in the African meningitis belt.

Background This systematic literature review aimed to summarize evidence for the added value of drug sales data analysis for the surveillance of infectious diseases. Methods A search for relevant publications was conducted in Pubmed, Embase, Scopus, Cochrane Library, African Index Medicus and Lilacs databases. Retrieved studies were evaluated in terms of objectives, diseases studied, data sources, methodologies and performance for real-time surveillance. Most studies compared drug sales data to reference surveillance data using correlation measurements or indicators of outbreak detection performance (sensitivity, specificity, timeliness of the detection). Results We screened 3266 articles and included 27 in the review. Most studies focused on acute respiratory and gastroenteritis infections. Nineteen studies retrospectively compared drug sales data to reference clinical data, and significant correlations were observed in 17 of them. Four studies found that over-the-counter drug sales preceded clinical data in terms of incidence increase. Five studies developed and evaluated statistical algorithms for selecting drug groups to monitor specific diseases. Another three studies developed models to predict incidence increase from drug sales. Conclusions Drug sales data analyses appear to be a useful tool for surveillance of gastrointestinal and respiratory disease, and OTC drugs have the potential for early outbreak detection. Their utility remains to be investigated for other diseases, in particular those poorly surveyed. Electronic supplementary material The online version of this article (doi:10.1186/s12879-014-0604-2) contains supplementary material, which is available to authorized users.