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

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

Understanding the spatio-temporal dynamics of meningitis epidemics outside the belt: the case of the Democratic Republic of Congo (DRC).

BACKGROUND: Bacterial meningitis remains a major threat for the population of the meningitis belt. Between 2004 and 2009, in the countries of this belt, more than 200,000 people were infected with a 10% mortality rate. However, for almost 20 years, important meningitis epidemics are also reported outside this belt. Research is still very poorly developed in this part of the word like in the Democratic Republic of Congo (DRC), which experiences recurrent epidemics. This article describes for the first time the spatio-temporal patterns of meningitis cases and epidemics in DRC, in order to provide new insights for surveillance and control measures. METHODS: Based on weekly suspected cases of meningitis (2000-2012), we used time-series analyses to explore the spatio-temporal dynamics of the disease. We also used both geographic information systems and geostatistics to identify spatial clusters of cases. Both using conventional statistics and the Cleveland's algorithm for decomposition into general trend, seasonal and residuals, we searched for the existence of seasonality. RESULTS: We observed a low rate of biological confirmation of cases (11%) using soluble antigens search, culture and PCR. The main strains found are Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis (A and C) serogroups. We identified 8 distinct spatial clusters, located in the northeastern and southeastern part of DRC, and in the capital city province, Kinshasa. A low seasonal trend was observed with higher incidence and attack rate of meningitis during the dry season, with a high heterogeneity in seasonal patterns occurring across the different districts and regions of DRC. CONCLUSION: Despite challenges related to completeness of data reporting, meningitis dynamics shows weak seasonality in DRC. This tends to suggest that climatic, environmental factors might be less preponderant in shaping seasonal patterns in central Africa. The characterization of 8 distinct clusters of meningitis could be used for a better sentinel meningitis surveillance and optimization of vaccine strategy in DRC. Improving biological monitoring of suspected cases should be a priority for future eco-epidemiological studies to better understand the emergence and spread of meningitis pathogens, and the potential ecological, environmental drivers of this disease.

Upper respiratory infections in a rural area with reduced malaria transmission in Senegal: a pathogens community study.

BACKGROUND: Acute Respiratory Infections (ARI) are common causes of febrile illnesses in many settings in Senegal. These infections are usually managed presumptively due to lack of appropriate diagnostic tools. This situation, can lead to poor management of febrile illness or antibiotic misuse. In addition, there are limited data on the spectrum of pathogens commonly responsible for these ARI. This study was conducted to explore the pathogens community among patients with acute respiratory infection in a rural area in Senegal. METHODS: A cross sectional study was conducted from August to December 2015. Children and adult patients attending Keur Socé health post for signs suggestive of acute respiratory infection were enrolled after providing inform consent. Eligible participants were recruited using a consecutive sampling method. Paired nose and throat swabs were collected for pathogen detection. Samples were processed using a multiplex PCR designed to identify 21 pathogens including both virus and bacteria. RESULTS: Two hundred and fifty patients participated in the study. Samples positivity rate was evaluated at 95.2% (238/250). Streptococcus pneumoniae was the predominant pathogen (74%) and was present in all months and all age-groups, followed by Staphylococcus aureus (28,8%) and rhinovirus (28,4%). Respiratory syncytial virus (RSV) was detected only among children under 5 years old in August and September while coronavirus was present in all age groups, during the months of October and December. CONCLUSION: This pilot study revealed a diversity of pathogens over the time and across all age groups, highlighting the need for further exploration. A pathogen community approach including both virus and bacteria at a larger scale becomes crucial for a better understanding of transmission dynamics at population level in order to help shape ARI control strategies.

Deciphering the impacts of vaccination and immunity on pertussis epidemiology in Thailand.

Pertussis is a highly infectious respiratory disease that is currently responsible for nearly 300,000 annual deaths worldwide, primarily in infants in developing countries. Despite sustained high vaccine uptake, a resurgence in pertussis incidence has been reported in a number of countries. This resurgence has led to critical questions regarding the transmission impacts of vaccination and pertussis immunology. We analyzed pertussis incidence in Thailand--both age-stratified and longitudinal aggregate reports--over the past 30 y. To dissect the contributions of waning pertussis immunity and repeat infections to pertussis epidemiology in Thailand following a pronounced increase in vaccine uptake, we used likelihood-based statistical inference methods to evaluate the support for multiple competing transmission models. We found that, in contrast to other settings, there is no evidence for pertussis resurgence in Thailand, with each model examined pointing to a substantial rise in herd immunity over the past 30 y. Using a variety of empirical metrics, we verified our findings by documenting signatures of changing herd immunity over the study period. Importantly, this work leads to the conclusion that repeat infections have played little role in shaping pertussis epidemiology in Thailand. Our results are surprisingly emphatic in support of measurable impact of herd immunity given the uncertainty associated with pertussis epidemiology.

Whooping cough dynamics in Chile (1932-2010): disease temporal fluctuations across a north-south gradient.

BACKGROUND: The spatial-temporal dynamics of Bordetella pertussis remains as a highly interesting case in infectious disease epidemiology. Despite large-scale vaccination programs in place for over 50 years around the world, frequent outbreaks are still reported in many countries. METHODS: Here, we use annual time series of pertussis incidence from the thirteen different regions of Chile (1952-2010) to study the spatial-temporal dynamics of Pertussis. The period 1975-1995 was characterized by a strong 4 year cycle, while the last two decades of the study period (1990-2010) were characterized by disease resurgence without significant periodic patterns. RESULTS: During the first decades, differences in periodic patterns across regions can be explained by the differences in susceptible recruitment. The observed shift in periodicity from the period 1952-1974 to the period 1975-1995 across regions was relatively well predicted by the susceptible recruitment and population size. However, data on vaccination rates was not taken into account in this study. CONCLUSIONS: Our findings highlight how demography and population size have interacted with the immunization program in shaping periodicity along a unique latitudinal gradient. Widespread B. pertussis vaccination appears to lead to longer periodic dynamics, which is line with a reduction in B. pertussis transmission, but our findings indicate that regions characterized by both low birth rate and population size decreased in periodicity following immunization efforts.

The niche reduction approach: an opportunity for optimal control of infectious diseases in low-income countries?

BACKGROUND: During the last century, WHO led public health interventions that resulted in spectacular achievements such as the worldwide eradication of smallpox and the elimination of malaria from the Western world. However, besides major successes achieved worldwide in infectious diseases control, most elimination/control programs remain frustrating in many tropical countries where specific biological and socio-economical features prevented implementation of disease control over broad spatial and temporal scales. Emblematic examples include malaria, yellow fever, measles and HIV. There is consequently an urgent need to develop affordable and sustainable disease control strategies that can target the core of infectious diseases transmission in highly endemic areas. DISCUSSION: Meanwhile, although most pathogens appear so difficult to eradicate, it is surprising to realize that human activities are major drivers of the current high rate of extinction among upper organisms through alteration of their ecology and evolution, i.e., their "niche". During the last decades, the accumulation of ecological and evolutionary studies focused on infectious diseases has shown that the niche of a pathogen holds more dimensions than just the immune system targeted by vaccination and treatment. Indeed, it is situated at various intra- and inter- host levels involved on very different spatial and temporal scales. After developing a precise definition of the niche of a pathogen, we detail how major advances in the field of ecology and evolutionary biology of infectious diseases can enlighten the planning and implementation of infectious diseases control in tropical countries with challenging economic constraints. SUMMARY: We develop how the approach could translate into applied cases, explore its expected benefits and constraints, and we conclude on the necessity of such approach for pathogen control in low-income countries.

The influence of geographic and climate factors on the timing of dengue epidemics in Perú, 1994-2008.

BACKGROUND: Dengue fever is a mosquito-borne disease that affects between 50 and 100 million people each year. Increasing our understanding of the heterogeneous transmission patterns of dengue at different spatial scales could have considerable public health value by guiding intervention strategies. METHODS: Based on the weekly number of dengue cases in Perú by province, we investigated the association between dengue incidence during the period 1994-2008 and demographic and climate factors across geographic regions of the country. RESULTS: Our findings support the presence of significant differences in the timing of dengue epidemics between jungle and coastal regions, with differences significantly associated with the timing of the seasonal cycle of mean temperature. CONCLUSIONS: Dengue is highly persistent in jungle areas of Perú where epidemics peak most frequently around March when rainfall is abundant. Differences in the timing of dengue epidemics in jungle and coastal regions are significantly associated with the seasonal temperature cycle. Our results suggest that dengue is frequently imported into coastal regions through infective sparks from endemic jungle areas and/or cities of other neighboring endemic countries, where propitious environmental conditions promote year-round mosquito breeding sites. If jungle endemic areas are responsible for multiple dengue introductions into coastal areas, our findings suggest that curtailing the transmission of dengue in these most persistent areas could lead to significant reductions in dengue incidence in coastal areas where dengue incidence typically reaches low levels during the dry season.

The environmental drivers of bacterial meningitis epidemics in the Democratic Republic of Congo, central Africa.

INTRODUCTION: Bacterial meningitis still constitutes an important threat in Africa. In the meningitis belt, a clear seasonal pattern in the incidence of meningococcal disease during the dry season has been previously correlated with several environmental parameters like dust and sand particles as well as the Harmattan winds. In parallel, the evidence of seasonality in meningitis dynamics and its environmental variables remain poorly studied outside the meningitis belt. This study explores several environmental factors associated with meningitis cases in the Democratic Republic of Congo (DRC), central Africa, outside the meningitis belt area. METHODS: Non-parametric Kruskal-Wallis' tests were used to establish the difference between the different health zones, climate and vegetation types in relation to both the number of cases and attack rates for the period 2000-2018. The relationships between the number of meningitis cases for the different health zones and environmental and socio-economical parameters collected were modeled using different generalized linear (GLMs) and generalized linear mixed models (GLMMs), and different error structure in the different models, i.e., Poisson, binomial negative, zero-inflated binomial negative and more elaborated multi-hierarchical zero-inflated binomial negative models, with randomization of certain parameters or factors (health zones, vegetation and climate types). Comparing the different statistical models, the model with the smallest Akaike's information criterion (AIC) were selected as the best ones. 515 different health zones from 26 distinct provinces were considered for the construction of the different GLM and GLMM models. RESULTS: Non-parametric bivariate statistics showed that there were more meningitis cases in urban health zones than in rural conditions (χ2 = 6.910, p-value = 0.009), in areas dominated by savannah landscape than in areas with dense forest or forest in mountainous areas (χ2 = 15.185, p-value = 0.001), and with no significant difference between climate types (χ2 = 1.211, p-value = 0,449). Additionally, no significant difference was observed for attack rate between the two types of heath zones (χ2 = 0.982, p-value = 0.322). Conversely, strong differences in attack rate values were obtained for vegetation types (χ2 = 13.627, p-value = 0,001) and climate types (χ2 = 13.627, p-value = 0,001). This work demonstrates that, all other parameters kept constant, an urban health zone located at high latitude and longitude eastwards, located at low-altitude like in valley ecosystems predominantly covered by savannah biome, with a humid tropical climate are at higher risk for the development of meningitis. In addition, the regions with mean range temperature and a population with a low index of economic well-being (IEW) constitute the perfect conditions for the development of meningitis in DRC. CONCLUSION: In a context of global environmental change, particularly climate change, our findings tend to show that an interplay of different environmental and socio-economic drivers are important to consider in the epidemiology of bacterial meningitis epidemics in DRC. This information is important to help improving meningitis control strategies in a large country located outside of the so-called meningitis belt.

Additional prognostic value of physical examination, exercise testing, and arterial ultrasonography for coronary risk assessment in primary prevention.

BACKGROUND: The choice of noninvasive tests used in primary prevention of cardiovascular diseases must be based on medical evidence. The aim of this study was to assess the additional prognostic value, over conventional risk factors, of physical examination, exercise testing, and arterial ultrasonography, in predicting a first coronary event. METHODS: A prospective cohort study was conducted between 1996 and 2004 (n = 2,709), with follow-up in 2006 (response rate 96.6%). Participants had no history or symptoms of cardiovascular disease and had a standardized physical examination, a cardiac exercise testing, and carotid and femoral ultrasonography at baseline. Incident cases of definite coronary events were recorded during follow-up. RESULTS: Over the Framingham risk score, femoral bruit, positive exercise test, intima-media thickness >0.63 mm, and a femoral plaque provided significant additional information to the prediction model. The addition of the exercise test to the traditional risk factors, then the intima-media thickness and lastly the presence of femoral plaques, produces incremental increases in the area under the receiver operating characteristic curve (0.73-0.78, P = .02) and about a 50% increase in the positive predictive value (15.8%-31.4%), with no effect on the negative predictive value (96.4%-96.9%). CONCLUSION: Physical examination, exercise testing, and arterial ultrasonography provide incremental information on the risk of coronary event in asymptomatic adults. Exercise testing and femoral ultrasonography also improve the accuracy of the risk stratification.

Relationships between climate and year-to-year variability in meningitis outbreaks: a case study in Burkina Faso and Niger.

BACKGROUND: Every year, West Africa is afflicted with Meningococcal Meningitis (MCM) disease outbreaks. Although the seasonal and spatial patterns of disease cases have been shown to be linked to climate, the mechanisms responsible for these patterns are still not well identified. RESULTS: A statistical analysis of annual incidence of MCM and climatic variables has been performed to highlight the relationships between climate and MCM for two highly afflicted countries: Niger and Burkina Faso. We found that disease resurgence in Niger and in Burkina Faso is likely to be partly controlled by the winter climate through enhanced Harmattan winds. Statistical models based only on climate indexes work well in Niger showing that 25% of the disease variance from year-to-year in this country can be explained by the winter climate but fail to represent accurately the disease dynamics in Burkina Faso. CONCLUSION: This study is an exploratory attempt to predict meningitis incidence by using only climate information. Although it points out significant statistical results it also stresses the difficulty of relating climate to interannual variability in meningitis outbreaks.

Comparative study of meningitis dynamics across nine African countries: a global perspective.

BACKGROUND: Meningococcal meningitis (MM) represents an important public health problem especially in the "meningitis belt" in Africa. Although seasonality of epidemics is well known with outbreaks usually starting in the dry season, pluri-annual cycles are still less understood and even studied. In this context, we aimed at study MM cases time series across 9 sahelo-sudanian countries to detect pluri-annual periodicity and determine or not synchrony between dynamics. This global and comparative approach allows a better understanding of MM evolution in time and space in the long-term. RESULTS: We used the most adapted mathematical tool to time series analyses, the wavelet method. We showed that, despite a strong consensus on the existence of a global pluri-annual cycle of MM epidemics, it is not the case. Indeed, even if a clear cycle is detected in all countries, these cycles are not as permanent and regular as generally admitted since many years. Moreover, no global synchrony was detected although many countries seemed correlated. CONCLUSION: These results of the first large-scale study of MM dynamics highlight the strong interest and the necessity of a global survey of MM in order to be able to predict and prevent large epidemics by adapted vaccination strategy. International cooperation in Public Health and cross-disciplines studies are highly recommended to hope controlling this infectious disease.

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

OBJECTIVES: Neisseria 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. METHODS: The literature was searched to provide a multi-disciplinary overview of the determinants of meningitis transmission dynamics in the African meningitis belt. RESULTS: Seasonal 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. CONCLUSIONS: Efforts 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.

Seasonal dynamics of bacterial meningitis: a time-series analysis.

BACKGROUND: Bacterial meningitis, which is caused mainly by Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae, inflicts a substantial burden of disease worldwide. Yet, the temporal dynamics of this disease are poorly characterised and many questions remain about the ecology of the disease. We aimed to comprehensively assess seasonal trends in bacterial meningitis on a global scale. METHODS: We developed the first bacterial meningitis global database by compiling monthly incidence data as reported by country-level surveillance systems. Using country-level wavelet analysis, we identified whether a 12 month periodic component (annual seasonality) was detected in time-series that had at least 5 years of data with at least 40 cases reported per year. We estimated the mean timing of disease activity by computing the centre of gravity of the distribution of cases and investigated whether synchrony exists between the three pathogens responsible for most cases of bacterial meningitis. FINDINGS: We used country-level data from 66 countries, including from 47 countries outside the meningitis belt in sub-Saharan Africa. A persistent seasonality was detected in 49 (96%) of the 51 time-series from 38 countries eligible for inclusion in the wavelet analyses. The mean timing of disease activity had a latitudinal trend, with bacterial meningitis seasons peaking during the winter months in countries in both the northern and southern hemispheres. The three pathogens shared similar seasonality, but time-shifts differed slightly by country. INTERPRETATION: Our findings provide key insight into the seasonal dynamics of bacterial meningitis and add to knowledge about the global epidemiology of meningitis and the host, environment, and pathogen characteristics driving these patterns. Comprehensive understanding of global seasonal trends in meningitis could be used to design more effective prevention and control strategies. FUNDING: Princeton University Health Grand Challenge, US National Institutes of Health (NIH), NIH Fogarty International Center Research and Policy for Infectious Disease Dynamics programme (RAPIDD), Bill & Melinda Gates Foundation.

Epidemiological impact of vaccination on the dynamics of two childhood diseases in rural Senegal.

Measles and pertussis are ubiquitous vaccine-preventable diseases, which remain an important public health problem in developing countries. Hence, developing a deep understanding of their transmission dynamics remains imperative. To achieve this, we compared the impact of vaccination at both individual and population levels in a Senegalese rural community. This study represents the first such comparative study in tropical conditions and constitutes a point of comparison with other studies of disease dynamics in developed countries. Changes in the transmission rates of infections are reflected in their mean ages at infection and basic reproductive ratio calculated before and after vaccination. We explored persistence of both infections in relation to population size in each village and found the inter-epidemic period for the whole area using wavelets analysis. As predicted by epidemiological theory, we observed an increase in the mean age at infection and a decrease in the reproductive ratio of both diseases. We showed for both the pre- vaccination and vaccine eras that persistence depends on population size. After vaccination, persistence decreased and the inter-epidemic period increased. The observed changes suggest that vaccination against measles and pertussis induced a drop in their transmission. Similarities in disease dynamics to those of temperate regions such as England and Wales were also observed.

Continuous subcutaneous insulin infusion versus multiple daily injections: the impact of baseline A1c.

OBJECTIVE: Rapid-acting insulin analogs (insulin lispro and insulin aspart) have emerged as the meal insulin of choice in both multiple daily insulin injection (MDII) therapy and continuous subcutaneous insulin infusion (CSII) for type 1 diabetes. Thus, a comparison of efficacy between CSII and MDII should be undertaken only in studies that used rapid-acting analogs for both intensive regimens. RESEARCH DESIGN AND METHODS: We performed a pooled analysis of the randomized controlled trials that compared CSII and optimized MDII therapy using rapid-acting analogs in adults with type 1 diabetes. RESULTS: The three studies that met inclusion criteria provided data on 139 patients, representing 596 patient-months for CSII and 529 patient-months for MDII. Mean age was 38.5 years, with duration of diabetes of 18.0 years. The studies differed significantly in mean baseline A1c (7.95, 8.20, and 9.27%). The pooled estimate of treatment effect comparing the percentage reduction in A1c by CSII with that by MDII (CSII - MDII) was 0.35% (95% CI -0.10 to 0.80, P = 0.08) using a random effect to account for heterogeneity between studies. Importantly, the interaction between baseline A1c and treatment modality emerged as an independent predictor of treatment effect (CSII - MDII) (P = 0.002). The relative benefit of CSII over MDII was found to increase with higher baseline A1c. A model derived from these data predicts that in a patient with a baseline A1c of 10%, CSII would reduce the A1c by an additional 0.65% compared with MDII. Conversely, there would be no A1c benefit of CSII compared with MDII if baseline A1c were 6.5%. There was no significant difference between CSII and MDII in the rate of hypoglycemic events. CONCLUSIONS: When using rapid-acting insulin analogs in CSII and MDII regimens in adult patients with type 1 diabetes, insulin pump therapy is associated with better glycemic control, particularly in those individuals with higher baseline A1c. Thus, CSII emerges as an important modality for implementing intensive therapy and may be uniquely advantageous in patients with poor glycemic control.

Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes: a randomized clinical trial.

OBJECTIVE: Insulin detemir is a soluble long-acting basal insulin analog designed to overcome the limitations of conventional basal insulin formulations. Accordingly, insulin detemir has been compared with NPH insulin with respect to glycemic control (HbA1c, prebreakfast glucose levels and variability, and hypoglycemia) and timing of administration. RESEARCH DESIGN AND METHODS: People with type 1 diabetes (n = 408) were randomized in an open-label, parallel-group trial of 16-week treatment duration using either insulin detemir or NPH insulin. Insulin detemir was administered twice daily using two different regimens, either before breakfast and at bedtime (IDet(morn+bed)) or at a 12-h interval (IDet(12h)). NPH insulin was administered before breakfast and at bedtime. Mealtime insulin was given as the rapid-acting insulin analog insulin aspart. RESULTS: With both insulin detemir groups, clinic fasting plasma glucose was lower than with NPH insulin (IDet(12h) vs. NPH, -1.5 mmol/l [95% CI -2.51 to -0.48], P = 0.004; IDet(morn+bed) vs. NPH, -2.3 mmol/l (-3.32 to -1.29), P < 0.001), as was self-measured prebreakfast plasma glucose (P = 0.006 and P = 0.004, respectively). The risk of minor hypoglycemia was lower in both insulin detemir groups (25%, P = 0.046; 32%, P = 0.002; respectively) compared with NPH insulin in the last 12 weeks of treatment, this being mainly attributable to a 53% reduction in nocturnal hypoglycemia in the IDet(morn+bed) group (P < 0.001). Although HbA1c for each insulin detemir group was not different from the NPH group, HbA1c for the pooled insulin detemir groups was significantly lower than for the NPH group (mean difference -0.18% [-0.34 to -0.02], P = 0.027). Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups (both P < 0.001). The NPH group gained weight during the study, but there was no change in weight in either of the insulin detemir groups (IDet(12h) vs. NPH, -0.8 kg [-1.44 to -0.24], P = 0.006; IDet(morn+bed) vs. NPH, -0.6 kg [-1.23 to -0.03], P = 0.040). CONCLUSIONS: Overall glycemic control with insulin detemir was improved compared with NPH insulin. The data provide a basis for tailoring the timing of administration of insulin detemir to the individual person's needs.

Whooping cough metapopulation dynamics in tropical conditions: disease persistence and impact of vaccination.

Recent insights in compiling metapopulation models and infectious disease dynamics have enabled a better understanding of spatial and temporal persistence of diseases. The concept of the critical community size (CCS) has been developed with major consideration on analyses of whooping cough and measles dynamics from temperate countries for which large datasets are available. However, few studies have questioned the generality of CCS curves for other regions, i.e. tropical areas, mainly because data are very sparse. This work constitutes, to our knowledge, the first study of whooping cough persistence in a tropical area, in a rural part of Senegal (Western Africa) where the population has been followed for 20 years. In this small community, the CCS is not reached even if we observe CCS-like curves showing persistence increasing with population size. In addition, our analysis supports the idea that vaccination has impacted the spatiotemporal dynamics and persistence of the disease. These findings suggest the need for more comparative analyses of spatio-temporal data series from a wide range of contrasted countries, for example developed and developing nations, so as to have a better understanding of vaccination effects on disease dynamics and persistence.

Spatial dynamics of pertussis in a small region of Senegal.

Extended time-series analysis of infectious diseases raises two issues: the spread of disease, and its persistence in space and time. Most studies are based on both data and models, corresponding to conditions encountered in developed countries. The present work sought to determine the impact of local heterogeneity on these two issues, regarding pertussis in tropical conditions. First, we tested the 'cities and villages' model in a small community of 30 villages in rural Senegal. Second, we focused on the impact of population size and density, as well as geographic distance, on population dynamics of pertussis. Results showed that pertussis initially arrived in urban centres, and then spread to surrounding areas. Both population size and density are implicated in the persistence of pertussis within the study area, whereas geographical distance between villages is not. This is the first study on pertussis in a developing country carried out on a very fine spatial scale. Furthermore, it confirms previous results for measles in England and Wales.

Timely detection of bacterial meningitis epidemics at district level: a study in three countries of the African Meningitis Belt.

BACKGROUND: Bacterial meningitis is a major public health problem in the African 'Meningitis Belt', where recurrent unpredictable epidemics occur. Despite the introduction in 2010 of the conjugate A vaccine, the reactive strategy remains important for responding to epidemics caused by other bacteria and in areas not yet vaccinated. Review of weekly numbers of suspected cases in Niger, Mali and Burkina Faso identified spatial disparities in the annual patterns of meningitis, which suggested a more local way of defining epidemics and initiating a timely vaccination campaign. METHOD: We defined an epidemic district-year as an excess of cases compared to the incidence previously experienced in the given district. Groups of similar districts in terms of seasonal patterns were identified by cluster analysis. We investigated a cluster-specific criterion of early epidemic onset to anticipate epidemic district-years. RESULTS: These were encouraging, as epidemic district-years were fairly efficiently captured, with an average time gained of 2.5 weeks over the current strategy. CONCLUSION: This early-onset criterion could help ensure timely implementation of vaccination campaigns without the need to modify the implemented surveillance system. The next step is to extend this study to other countries of the Meningitis Belt, and to explain the differences in seasonal patterns in the different clusters.

Arterial ultrasound screening as a tool for coronary risk assessment in asymptomatic men and women.

One of the imaging tests most commonly used to assess cardiovascular diseases (CVDs) in daily practice is Doppler ultrasonography of the carotid and femoral arteries. We included 2709 participants with no history or symptoms of CVD; they had a risk factor assessment and a carotid and femoral ultrasonography at baseline. Incident cases of definite coronary events were recorded during a median follow-up of 6 years. Approximately, 63% of the sample presented abnormalities (carotid stenosis >50%, carotid plaque, femoral plaque, increased intima-media thickness [IMT]). A moderately increased IMT (>0.63 mm) or the presence of carotid or femoral artery plaque was related to prognosis. The associations persisted after adjustment for pretest risk, treatment with statins, and other Doppler ultrasonography abnormalities. The hazard ratio increased significantly with the number of abnormalities (varying from 2.35 [1.16-4.74] to 14.83 [6.47-33.9]).