Judith E. Mueller

Emergence of serogroup X meningococcal disease in Africa: need for a vaccine.

Neisseria meningitidis is responsible for the seasonal burden and recurrent epidemics of meningitis in an area of sub-Saharan Africa known as the meningitis belt. Historically, the majority of the cases in the meningitis belt are caused by serogroup A meningococci. Serogroup C meningococci were responsible for outbreaks in the meningitis belt in the 1980s, while serogroup W (formerly W-135) has emerged as a cause of epidemic meningitis since 2000. Serogroup X meningococci have previously been considered a rare cause of sporadic meningitis, but during 2006-2010, outbreaks of serogroup X meningitis occurred in Niger, Uganda, Kenya,Togo and Burkina Faso, the latter with at least 1300 cases of serogroup X meningitis among the 6732 reported annual cases. While serogroup X has not yet caused an epidemic wave of the scale of serogroup A in 1996-1997 or serogroup W in Burkina Faso during 2002, the existing reports suggest a similar seasonal hyperendemicity and capacity for localised epidemics. Serogroup X incidence appears to follow a pattern of highly localised clonal waves, and in affected districts, other meningococcal serogroups are usually absent from disease. Currently, no licensed vaccine is available against serogroup X meningococci. Following the introduction of a monovalent serogroup A conjugate vaccine (MenAfriVac(®)) in the meningitis belt and the upcoming introduction of pneumococcal conjugate vaccines, vaccine-based prevention of serogroup X may become a public health need. The serogroup X polysaccharide capsule is the most likely target for vaccine development, but recent data also indicate a potential role for protein-based vaccines. A multivalent vaccine, preferably formulated as a conjugate vaccine and covering at least serogroups A, W, and X is needed, and the efforts for vaccine development should be intensified.

Seroprevalence of Bactericidal, Specific IgG Antibodies and Incidence of Meningitis Due to Group A Neisseria meningitidis by Age in Burkina Faso 2008

Background We investigated serological correlates of protection against Neisseria meningitidis serogroup A (NmA) in Burkina Faso before the introduction of NmA conjugate vaccine. Methodology/Principal Findings We collected blood from a representative sample (Nu200a=u200a1022) of Bobo-Dioulasso residents. Sera were evaluated for serum bactericidal antibody (SBA) activity against NmA strains of immunotype L11 (F8238) and L10 (3125) and NmA-specific IgG. Seroprevalence was compared to the age-specific NmA meningitis incidence in Bobo-Dioulasso during March 2007–February 2008. Meningococcal carriage was evaluated in a subset (Nu200a=u200a538). Geometric mean titres (GMT)/concentrations (GMC) of SBA and NmA-specific IgG increased with age, peaking around age 20 years. Overall, 70% of our sample had NmA-specific IgG ≥2 ug/mL. Meningitis incidence was highest in those aged <6 months and 5–19 years. No NmA carriers were found. Compared to the reference strain SBA, GMTs were higher against a locally isolated strain and around 40-fold lower against Dutch strain 3125. Conclusions/Significance This study provides estimates of natural immunity to NmA, according to a variety of antibody measures, which will be helpful in ascertaining antibody persistence after MenAfriVac™ introduction. Age-specific seroprevalence of reference strain SBA titres most likely reflects exposure to meningococci and consecutive reactive immunity. We could not define any serological correlate of protection.

Incidence, Carriage and Case-Carrier Ratios for Meningococcal Meningitis in the African Meningitis Belt: A Systematic Review and Meta-Analysis

Background To 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. Methods We 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). Findings Eight 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. u2028For 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. Conclusion Seasonal 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.

Towards understanding the epidemiology of Neisseria meningitidis in the African meningitis belt: a multi-disciplinary overview.

OBJECTIVESnNeisseria meningitidis is the major cause of seasonal meningitis epidemics in the African meningitis belt. In the changing context of a reduction in incidence of serogroup A and an increase in incidence of serogroups W and C and of Streptococcus pneumoniae, a better understanding of the determinants driving the disease transmission dynamics remains crucial to improving bacterial meningitis control.nnnMETHODSnThe literature was searched to provide a multi-disciplinary overview of the determinants of meningitis transmission dynamics in the African meningitis belt.nnnRESULTSnSeasonal hyperendemicity is likely predominantly caused by increased invasion rates, sporadic localized epidemics by increased transmission rates, and larger pluri-annual epidemic waves by changing population immunity. Carriage likely involves competition for colonization and cross-immunity. The duration of immunity likely depends on the acquisition type. Major risk factors include dust and low humidity, and presumably human contact rates and co-infections; social studies highlighted environmental and dietary factors, with supernatural explanations.nnnCONCLUSIONSnEfforts should focus on implementing multi-country, longitudinal seroprevalence and epidemiological studies, validating immune markers of protection, and improving surveillance, including more systematic molecular characterizations of the bacteria. Integrating climate and social factors into disease control strategies represents a high priority for optimizing the public health response and anticipating the geographic evolution of the African meningitis belt.

Knowledge of obstetric fistula prevention amongst young women in urban and rural Burkina Faso: a cross-sectional study.

Obstetric fistula is a sequela of complicated labour, which, if untreated, leaves women handicapped and socially excluded. In Burkina Faso, incidence of obstetric fistula is 6/10,000 cases amongst gynaecological patients, with more patients affected in rural areas. This study aims to evaluate knowledge on obstetric fistula among young women in a health district of Burkina Faso, comparing rural and urban communities. This cross-sectional study employed multi-stage sampling to include 121 women aged 18-20 years residing in urban and rural communities of Boromo health district. Descriptive statistics and multiple logistic regression analysis were used to compare differences between the groups and to identify predictors of observed knowledge levels. Rural women were more likely to be married (p<0.000) and had higher propensity to teenage pregnancy (p=0.006). The survey showed overall poor obstetric fistula awareness (36%). Rural residents were less likely to have adequate preventive knowledge than urban residents [OR=0.35 (95%-CI, 0.16–0.79)]. This effect was only slightly explained by lack of education [OR=0.41 (95%-CI, 0.18–0.93)] and only slightly underestimated due to previous pregnancy [OR=0.27 (95%-CI, 0.09–0.79)]. Media were the most popular source of awareness amongst urban young women in contrast to their rural counterparts (68% vs. 23%). Most rural young women became ‘aware’ through word-of-mouth (68% vs. 14%). All participants agreed that the hospital was safer for emergency obstetric care, but only 11.0% believed they could face pregnancy complications that would require emergency treatment. There is urgent need to increase emphasis on neglected health messages such as the risks of obstetric fistula. In this respect, obstetric fistula prevention programs need to be adapted to local contexts, whether urban or rural, and multi-sectoral efforts need to be exerted to maximise use of other sectoral resources and platforms, including existing routine health services and schools, to ensure sustainability of health literacy efforts.

Drug sales data analysis for outbreak detection of infectious diseases: a systematic literature review

BackgroundThis systematic literature review aimed to summarize evidence for the added value of drug sales data analysis for the surveillance of infectious diseases.MethodsA 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).ResultsWe 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.ConclusionsDrug 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.

Surveillance of gastrointestinal disease in France using drug sales data

Drug sales data have increasingly been used for disease surveillance during recent years. Our objective was to assess the value of drug sales data as an operational early detection tool for gastroenteritis epidemics at national and regional level in France. For the period 2008-2013, we compared temporal trends of drug sales for the treatment of gastroenteritis with trends of cases reported by a Sentinel Network of general practitioners. We benchmarked detection models to select the one with the best sensitivity, false alert proportion and timeliness, and developed a prospective framework to assess the operational performance of the system. Drug sales data allowed the detection of seasonal gastrointestinal epidemics occurring in winter with a distinction between prescribed and non-prescribed drugs. Sales of non-prescribed drugs allowed epidemic detection on average 2.25 weeks earlier than Sentinel data. These results confirm the value of drug sales data for real-time monitoring of gastroenteritis epidemic activity.

Natural immunity against capsular group X N. meningitidis following an outbreak in Togo, 2007.

BACKGROUNDnCapsular 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 3-5u202fyears, 100 aged 13-19u202fyears and 100 aged 20-25u202fyears) were included in the study, and serum responses were compared with sera from age-matched controls from the U.K. and Burkina Faso.nnnMETHODSnMenX serum bactericidal antibody (SBA) was measured using rabbit complement, and antibodies against MenX polysaccharide (XPS) and outer membrane vesicles (XOMVs) were quantified by ELISA.nnnRESULTSnThe 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 3-5u202fyears, 34% (95% CI 9-60) among those aged 13-19u202fyears and 32% (95% CI 24-40) among those aged 20-25u202fyears. These were significantly higher than observed in the control populations from the U.K (range 13-16%) and Burkina Faso (range 2-6%).nnnCONCLUSIONnIn 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.

Quantifying population preferences around vaccination against severe but rare diseases: A conjoint analysis among French university students, 2016

BACKGROUNDnSeveral 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.nnnMETHODSnDuring March-May 2016, we conducted an emailing survey among university students aged 18-24years (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.nnnRESULTSnParticipants 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).nnnCONCLUSIONSnAmong 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.

Evaluation of response strategies against epidemics due to Neisseria meningitidis C in Niger

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.