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Introduction The 2009 influenza pandemic highlighted challenges for vaccine post-marketing monitoring in Europe, particularly the need to have appropriate infrastructures to strengthen public-private collaborations (PPCs) with suitable processes to improve stakeholder interactions and collection and analysis of safety and effectiveness data. The ADVANCE consortium comprises public and private stakeholders who have worked together to build and test new system components for vaccine post-marketing projects, one component being a governance framework for efficient, transparent and trustworthy PPCs. Methods Based on the results of a landscape analysis and screening of formalised existing governance structures, we identified the elements of a governance framework and developed recommendations to support stakeholders willing and able to implement collaborative projects. These proposals and their implementation were discussed by 70 experts during a workshop to gain from their experience. Results We identified core governance principles and defined five fundamental functions (decision-making, scientific advice, quality control and audit, implementation and management, and financial administration) that can be attributed to individual partner organisations or to a committee with representatives from more than one partner organisation. We propose a generic governance model with options for its adaptation to specific contexts and projects. The advantages and disadvantages of PPCs were also examined. Stakeholders’ concerns (e.g. scientific integrity and public trust) were addressed through recommendations about transparent decision-making rules and conflict of interest management. Conclusions No one-size-fits-all solution for PPC governance exists but our recommendations could be used to set-up a tailored-made and fully transparent governance structure supporting collaborative projects in the European vaccine post-marketing environment. To allow the rapid establishment of robust projects, the next steps will involve this guidance being used by real-world collaborations to assess what works and what does not work and what added-value can be obtained from these collaborations.

Lessons learnt from the 2009 (H1N1) flu pandemic highlighted factors limiting the capacity to collect European data on vaccine exposure, safety and effectiveness, including lack of rapid access to available data sources or expertise, difficulties to establish efficient interactions between multiple parties, lack of confidence between private and public sectors, concerns about possible or actual conflicts of interest (or perceptions thereof) and inadequate funding mechanisms. The Innovative Medicines Initiative's Accelerated Development of VAccine benefit-risk Collaboration in Europe (ADVANCE) consortium was established to create an efficient and sustainable infrastructure for rapid and integrated monitoring of post-approval benefit-risk of vaccines, including a code of conduct and governance principles for collaborative studies. The development of the code of conduct was guided by three core and common values (best science, strengthening public health, transparency) and a review of existing guidance and relevant published articles. The ADVANCE Code of Conduct includes 45 recommendations in 10 topics (Scientific integrity, Scientific independence, Transparency, Conflicts of interest, Study protocol, Study report, Publication, Subject privacy, Sharing of study data, Research contract). Each topic includes a definition, a set of recommendations and a list of additional reading. The concept of the study team is introduced as a key component of the ADVANCE Code of Conduct with a core set of roles and responsibilities. It is hoped that adoption of the ADVANCE Code of Conduct by all partners involved in a study will facilitate and speed-up its initiation, design, conduct and reporting. Adoption of the ADVANCE Code of Conduct should be stated in the study protocol, study report and publications and journal editors are encouraged to use it as an indication that good principles of public health, science and transparency were followed throughout the study.

Introduction: A second generation HPV vaccine has been developed for the prevention of anogenital cancers and precancerous lesions of the cervix, vulva, vagina, anus and of genital warts due to nine HPV types.We estimated the annual burden of these diseases attributable to the nine HPV types compared to HPV types from first generation vaccines in women and men in Europe. Material and methods: Incidence rates from the IARC database, cancer registries, the literature and Eurostat population data were used.The burden attributable to the HPV types targeted by both vaccines was estimated by applying the relative contribution of the respective HPV types from epidemiological studies. Results: In 2013, the number of new anogenital HPV-attributable cancers was 44,480 with 39,494 of these cases related to second vs. 33,285 to first generation vaccine types.Among the 284,373 to 541,621 new HPV-attributable anogenital precancerous lesions 235,364–448,423 and 135,025–256,830 were estimated to be related to second and first generation vaccine types, respectively.The annual number of new genital warts was 753,608–935,318, with 90% related to HPV6/11. Conclusions: These data demonstrate how the large public health impact that was achieved by the first generation HPV vaccines could be further increased by second generation vaccines. Keywords: HPV, Burden of disease, Cancer, Precancerous lesions, Genital warts, HPV vaccine

Objectives: To quantify the benefit–risk (BR) balance of the quadrivalent human papillomavirus (qHPV) vaccine for use in males, including anal cancer prevention, by using the multicriteria decision analysis (MCDA).Methods: Value tree and an effect table were compiled using relevant qHPV vaccine efficacy/safety data. An expert panel validated the final model inputs.Results: On a scale of 0–100, the MCDA qHPV vaccine score (66) was superior to the no vaccination score (46), indicating a more favorable BR balance for the qHPV vaccine. Significant changes in weight of individual outcomes were needed to change BR balance in sensitivity analyses. The qHPV vaccine maintained a better BR profile in all alternative models.Conclusions: MCDA can be used to transparently evaluate BR balance of vaccines. The qHPV vaccine had a favorable BR balance in males. Including anal cancer as a new indication further improves the BR profile of the qHPV vaccine.

Key points The effectiveness of pentavalent rotavirus vaccine against rotavirus-associated hospitalization was more than 90% 4 years after introduction into the national immunization program in Finland. A major impact on hospitalization for all-cause gastroenteritis was observed also. Background Rotavirus vaccination with exclusive use of RotaTeq was added to the National Immunization Programme (NIP) of Finland in September 2009. The objective of our study was to estimate the effectiveness and impact of RotaTeq after 4 years of follow-up. Methods Between 2009 and 2013, we conducted a prospective surveillance study of children aged 95%) has led to a major reduction in RV-AGE and AC-AGE hospitalizations without a resurgence of rotavirus activity. However, rotavirus continues to circulate in older unvaccinated children.

Immunisation Information Systems (IIS) are computerised confidential population based-systems containing individual-level information on vaccines received in a given area. They benefit individuals directly by ensuring vaccination according to the schedule and they provide information to vaccine providers and public health authorities responsible for the delivery and monitoring of an immunisation programme. In 2016, the European Centre for Disease Prevention and Control (ECDC) conducted a survey on the level of implementation and functionalities of IIS in 30 European Union/European Economic Area (EU/EEA) countries. It explored the governance and financial support for the systems, IIS software, system characteristics in terms of population, identification of immunisation recipients, vaccinations received, and integration with other health record systems, the use of the systems for surveillance and programme management as well as the challenges involved with implementation. The survey was answered by 27 of the 30 EU/EEA countries having either a system in production at national or subnational levels (n = 16), or being piloted (n = 5) or with plans for setting up a system in the future (n = 6). The results demonstrate the added-value of IIS in a number of areas of vaccination programme monitoring such as monitoring vaccine coverage at local geographical levels, linking individual immunisation history with health outcome data for safety investigations, monitoring vaccine effectiveness and failures and as an educational tool for both vaccine providers and vaccine recipients. IIS represent a significant way forward for life-long vaccination programme monitoring.

Background: The Guillain-Barré syndrome (GBS) occurs after infections and as an adverse reaction to vaccines. No detailed information on incidence rates (IRs) in Germany is available. Methods: This retrospective cohort study estimated age- and sex-specific IRs of GBS in Germany in the years 2007-2009 based on electronic healthcare data from the German Pharmacoepidemiological Research Database (GePaRD). Two case definitions were applied. GBS cases had a main discharge diagnosis of GBS. GBS_PROCEDURE cases in addition had codes for relevant diagnostic procedures. Crude and standardized IRs (SIRs) with 95% confidence intervals were stratified by year, age group, sex, region and season. IR ratios (IRRs) for each stratification factor were calculated by multivariable Poisson regression. Results: Among 13,297,678 persons, 889 (693) incident GBS (GBS_PROCEDURE) cases were identified. Overall SIRs per 100,000 person years were 2.4 (2.2-2.5) for GBS and 1.8 (1.7-2.0) for GBS_PROCEDURE. (S)IRs increased with age, peaking in the age group 70-79 years (IR GBS: 5.5 (4.7-6.5)) and were higher in males than in females (e.g., IR GBS: IRR = 1.5 (1.3-1.7)) and in February-April, as compared to the rest of the year. No regional pattern was observed. Conclusion: (S)IRs of GBS in Germany differed by age, sex and season and were comparable to those found in other studies. Results might be used as a comparator in vaccine safety monitoring.

Introduction Observational studies are widely used to evaluate the impact of vaccines. They are being conducted by a variety of institutions and collaborations, including public-private partnerships (PPPs). The European Union promotes PPPs through the Innovative Medicines Initiative (IMI): examples of its vaccine-related IMI PPPs include the ADVANCE and DRIVE consortia (respectively, Accelerated Development of VAccine benefit–risk Collaboration in Europe & Development of Robust and Innovative Vaccine Effectiveness). However, practices and attitudes towards PPPs in the public health field differ, and concerns over their scientific independence have been put forth. While there have been efforts to evaluate and strengthen the methodology and reporting of observational studies, clear and comprehensive guidelines on how to evaluate their scientific independence, integrity and transparency (especially in the presence of diverse governance and funding models) are lacking. Methods A review of existing guidelines touching upon the topics of scientific independence, integrity and/or transparency in the context of observational studies was performed (consisting of a literature search and screening of the reference lists of retrieved documents). Key indicators of scientific independence, integrity and transparency were identified with the focus on relevance and measurability. Based on these, a checklist for evaluating individual studies and study protocols has been compiled. Results Several guidelines include recommendations on topics related to scientific independence, integrity and transparency that can be applied to observational studies of vaccines’ impact. The ADVANCE Code of Conduct was selected as the pivotal reference as it already considered relevant guidelines during its preparation; examples of these include the International Epidemiological Association's Good Epidemiological Practice (GEP) and the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) Checklist for Study Protocols. We present an overview of the various definitions and principles, as well as a checklist-based tool for evaluating the scientific independence, integrity and transparency of observational studies. The tool can be applied by independent reviewers to assess studies retrospectively as well as by study teams to inform the planning of new ones. Conclusions Questions of scientific independence, integrity and transparency are central in evaluating evidence from observational studies of vaccines. Our tool aims to provide a systematic way to address these topics; the next step will be to validate it in relation to existing protocols.

Summary Objective The development of a biomarker of exposure based on the evaluation of the human antibody response specific to Anopheles salivary proteins seems promising in improving malaria control. The IgG response specific to the gSG6-P1 peptide has already been validated as a biomarker of An. gambiae exposure. This study represents a first attempt to validate the gSG6-P1 peptide as an epidemiological tool evaluating exposure to An. funestus bites, the second main malaria vector in sub-Saharan Africa. Methods A multi-disciplinary survey was performed in a Senegalese village where An. funestus represents the principal anopheline species. The IgG antibody level specific to gSG6-P1 was evaluated and compared in the same children before, at the peak and after the rainy season. Results Two-thirds of the children developed a specific IgG response to gSG6-P1 during the study period and – more interestingly – before the rainy season, when An. funestus was the only anopheline species reported. The specific IgG response increased during the An. funestus exposure season, and a positive association between the IgG level and the level of exposure to An. funestus bites was observed. Conclusions The results suggest that the evaluation of the IgG response specific to gSG6-P1 in children could also represent a biomarker of exposure to An. funestus bites. The availability of such a biomarker evaluating the exposure to both main Plasmodium falciparum vectors in Africa could be particularly relevant as a direct criterion for the evaluation of the efficacy of vector control strategies. Premiere tentative de validation du peptide salivaire gSG6-P1 comme un outil immuno-epidemiologique d’evaluation de l’exposition humaine aux piqures de An. funestus Objectif: Valider le peptide gSG6-P1 comme un outil epidemiologique evaluant l’exposition aux piqures de An. funestus, le second principal vecteur de la malaria en Afrique subsaharienne. Methodes: Etude multidisciplinaire dans un village senegalais ouAn. funestus est la principale espece d’anophele. Le taux d’anticorps IgG specifiques a gSG6-P1 a eteevalue et compare chez les memes enfants avant, durant le pic et a la fin de la saison des pluies. Resultats: Deux tiers des enfants ont developpe une reponse IgG specifique a gSG6-P1 durant la periode etudiee et - plus interessant - avant la saison des pluies, quand An. funestus etait la seule espece d’anophele signalee. La reponse IgG specifique augmentait au cours de saison d’exposition a l’An. funestus et une association positive entre le taux d’IgG et le niveau d’exposition aux piqures de An. funestus a ete observee. Conclusions: Les resultats suggerent que l’evaluation de la reponse IgG specifique a gSG6-P1 chez les enfants pourrait egalement representer un biomarqueur de l’exposition aux piqures de An. funestus. La disponibilite d’un tel biomarqueurs evaluant l’exposition aux deux principaux vecteurs de P. falciparum en Afrique pourrait etre particulierement pertinente en tant que critere pour l’evaluation directe de l’efficacite des strategies de lutte antivectorielle. Primer ensayo para validar el peptido salivar gSG6-P1 como herramienta inmuno-epidemiologica que evalue la exposicion humana frente a picaduras de An. funestus Objetivo: Validar el peptido gSG6-P1 como herramienta epidemiologica que evalue la exposicion a picaduras de An. funestus, el segundo vector de malaria mas importante en Africa sub-Sahariana. Metodos: Estudio multidisciplinar, en un poblado senegales en donde An. funestus es la principal especie anofelina. Los niveles de anticuerpos IgG especificos para gSG6-P1 se evaluaron y compararon en los mismos ninos antes, durante el pico y despues de la estacion de lluvias. Resultados: Dos tercios de los ninos desarrollaron una IgG especifica para gSG6-P1 durante el periodo de estudio y – mas interesante aun – antes de la epoca lluviosa, cuando An. funestus era la unica especie anofelina reportada. La respuesta IgG especifica aumento durante el periodo de exposicion a An. funestus y se observo una asociacion positiva entre el nivel de IgG y el nivel de exposicion a picaduras de An. funestus. Conclusiones: Los resultados sugieren que la evaluacion de la respuesta IgG especifica para gSG6-P1 en ninos tambien podria utilizarse como un biomarcador de exposicion a picaduras de An. funestus. La disponibilidad de un biomarcador que evalua la exposicion a los dos principales vectores de P. falciparum en Africa podria ser particularmente relevante como un criterio directo para la evaluacion de la eficacia de estrategias de control vectorial.

Aedes mosquitoes are the major vectors of (re)-emerging infections including arboviruses (dengue, Chikungunya, yellow fever) in developing countries. Moreover, the emergence of Aedes-borne diseases in the developed world is currently a source of concern. Evaluation of human immune responses to Aedes bites could be a useful immuno-epidemiological tool for evaluating exposure to Aedes-borne diseases and thus predicting the risk of such emerging diseases. Specific IgE and IgG4 antibody (Ab) responses to Aedes aegypti saliva were evaluated in young Senegalese children living in an area of exposure to the Aedes vector. Specific IgE and IgG4 responses increased during rainy season of high exposure to Aedes bites. In addition, the evolution of anti-saliva isotype levels during the rainy season presented spatial heterogeneity between the studied villages. These preliminaries results support the potential approach of using anti-saliva Ab responses for evaluating exposure to Aedes vectors and risks of emerging arbovirus infections.

Negative consequences of malaria might account for seasonality in nutritional status in children in the Sahel. We report the impact of a randomized, double-blind, placebo-controlled trial of seasonal intermittent preventive anti-malarial treatment on growth and nutritional status in 1,063 Senegalese preschool children. A combination of artesunate and sulfadoxine-pyrimethamine was given monthly from September to November. In the intervention arm, mean weight gain was significantly greater (122.9 ± 340 versus 42.9 ± 344 [SD] g/mo, P < 0.0001) and losses in triceps and subscapular skinfold measurements were less (−0.39 ± 1.01 versus −0.66 ± 1.01 mm/mo, and −0.15 ± 0.64 versus −0.36 ± 0.62 mm/mo, respectively, P < 0.0001 for both). There was no difference in height increments. The prevalence of wasting increased significantly in the control arm (4.6% before versus 9.5% after, P < 0.0001), but remained constant in intervention children: 5.6% versus 7.0% (P = 0.62). The prevention of malaria would improve child nutritional status in areas with seasonal transmission.

Available data on the long-term consequences of preschool stunting are scarce and conflicting. The objective of this study was to assess the amount of catch-up growth from preschool stunting and the effect of migration (change in environment) during adolescence. A cohort study from preschool age (1‐5 y) to adulthood (18‐23 y) was conducted among 2874 subjects born in a rural area of Senegal. The subjects were divided into 3 groups of preschool stunting: none, mild, and marked, with height-for-age Z-scores of .21, 2 2t o21, and ,22, respectively. At follow-up, the history of migration was recalled. Mean height was 161.3 cm for girls and 174.0 cm for boys ($20 y). Stunted subjects remained smaller than the others: the age-adjusted height deficit between the 2 extreme categories was 6.6 and 9.0 cm in girls and boys, respectively. However, their height increment from early childhood to adulthood differed (69.3, 70.5, and 72.0 cm, P ¼ 0.0001, and 78.9, 80.0, and 80.3 cm, P , 0.01, for nonstunted, mildly stunted, and markedly stunted girls and boys, respectively). The duration of labor migration to the city was associated with height increment in girls only in a nonlinear relation (adjusted means: 67.2, 69.3, 67.4, and 67.7 cm for 4 groups of increasing duration, P , 0.01). In conclusion, Senegalese children caught up in height prior to adulthood, with the adult means ;2 cm below the WHO/NCHS reference. However, this global catch up did not reduce height differences between formerly stunted and nonstunted children to any greater extent and it was not enhanced by labor migration. J. Nutr. 136: 2412‐2420, 2006.

Despite intense efforts to maintain a high level of vaccine coverage against human whooping cough, rural senegalese areas are still endemic for Bordetella pertussis. One explanation being the potential existence of animal reservoirs, the objective of this work was to precise the carriage by domestic animals of bacteria belonging to the genus Bordetella in Senegal. Bacteriological samples (swabs and aspirates) were obtained from various domestic animals living in different parts of the country. No B. pertussis nor B. parapertussis were isolated. However, for the first time to our knowledge, B. bronchiseptica was identified from small ruminants located in Africa. The positive animals were two goats and two sheep from Dakar slaughterhouse together with a goat living in a rural compound. The fact that it was identified in goats and sheep underlines the potential zoonotic of that bacterial species in countries where small ruminants are of economical and cultural relevance.

Early supplementation of breastfed infants may have consequences both for the mother and the child. We hypothesised that it would result in decreased maternal weight loss and in shorter durations of breastfeeding and birth intervals. Controlled randomised population-based trial. Six villages in the Sine area of Senegal, West Africa. Healthy breastfed infants and their mothers, 68 controls and 66 supplemented infants at randomization. Supplementation with high-energy, nutrient dense food from 4 to 7 months of age, twice daily under supervision of field workers. Both controls and supplemented infants were free to eat other complementary foods. Maternal weight was measured monthly. Dates of breastfeeding cessation and of subsequent births were collected prospectively through weekly demographic surveillance, and were analysed using Cox's regression models and ‘intent-to-supplement’ approach. Mean maternal weight gain from 4 to 7 months postpartum tended to be greater in the supplemented group (+0.25 kg/months, 95% confidence interval (CI): −0.07, +0.57). Supplemented infants were breastfed for significantly longer durations than controls (medians: 24.9 and 23.7 months, respectively, P: 0.034). Their adjusted hazard ratio (HR) for breastfeeding cessation was 0.59 (95% CI: 0.40, 0.89). Their mothers had a lower risk of a new birth than mothers of controls (adjusted HR: 0.57, 95% CI: 0.36, 0.92). Early short-term infant supplementation tended to decrease maternal postpartum weight loss, but it increased, rather than shortened, the duration of breastfeeding and birth interval. This study was supported by a grant from the French Ministry of Research (Grant 92L0623).

Pertussis is a worldwide infectious disease which persists despite massive vaccination campaigns that have gone on for several decades. To obtain an overall view of pertussis dynamics and the impact of vaccination, the authors performed, using the wavelet method, a comparative analysis of pertussis time series in 12 countries to detect and quantify periodicity and synchrony between them. Results showed a clear 3- to 4-year cycle in all countries, but the main finding was that this periodicity was transient. No global pattern in the effect of vaccination on pertussis dynamics was observed, but some spatial synchrony between countries was detected. This large-scale comparative analysis of pertussis dynamics sheds light on the complexity of the multiple interactions involved in global pertussis spatial dynamic patterns. It suggests a need to perform a global survey of human infectious diseases over the long term, which would permit better assessment of the risk of disease outbreaks in the future.

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.

Ruel and Menon recently published a young child feeding index based on characteristics taken from 24-h and 7-d recalls. A strong positive association was found in 7 Latin American Demographic and Health Surveys for 12- to 36-mo-old children (1). The aim of this study was to test for associations of this index with height-for-age and linear growth in African children. Children (n = 500), aged 12-42 mo, living in a rural area of Senegal were visited in their homes in April-May, and 24-h and 7-d food recalls were conducted with their mothers. Height was measured, and measurements taken 7 mo earlier were used to compute linear growth rates. General linear models were used to adjust for potential confounders (child age and sex, maternal height, BMI, and socioeconomic status). The feeding index was not associated with either height-for-age (adjusted means: -1.01, -1.06, and -1.20 Z-scores for the 1st, 2nd, and 3rd tercile, respectively) or with linear growth (6.2, 6.0, and 6.3 cm/7 mo for the 3 terciles, respectively). Continuing breast-feeding was negatively associated with height-for-age (P < 0.05) and positively associated with linear growth (P < 0.01). Frequent consumption of fruit was positively associated with both (P = 0.059 and P = 0.027, respectively, in adjusted models), whereas food consumption from an animal source was not. In conclusion, the composite feeding index was independent of height and linear growth in these rural African children, due in part to reverse causality between breast-feeding duration and stunting.

Although use of acellular pertussis vaccine was associated with a higher rate of vaccine failure than that of whole-cell vaccine in the Senegal Pertussis Trial conducted in 1990-1994 on 4189 children, risk factors for vaccine failure regarding exposure and susceptibility to pertussis have not been studied so far. Pertussis occurred in 346 vaccinated children. Three factors were found to be associated with vaccine failure, independently of the vaccine type, namely the degree of exposure, birth rank, and time since weaning. In the whole-cell vaccine group, the risk of failure increased with birth rank [RR = 2.95 (1.51-5.75)] and was higher in non stunted children [RR = 1.43 (1.05-1.94)]. In the acellular vaccine group, the risk of failure increased with age at exposure to B. pertussis [RR = 2.24 (1.21-4.12) after 18 months of age] and the degree of exposure [RR = 2.14 (1.17-3.93) when the child shared the hut of an index case]. These results highlight the influence of environmental factors on the success of pertussis vaccination. However, they do not explain the shorter duration of protection provided by the acellular vaccine compared to the whole-cell vaccine which persist after controlling and thus might be related to the nature of the vaccine.

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.

In 1989, high-titer (HT) Edmonston-Zagreb measles vaccine with a titer more than 10(4.7) plaque-forming-units was recommended by the World Health Organization for use in areas with a high incidence of measles in children younger than 9 months. In 1992, the recommendation was rescinded following reports from Guinea-Bissau, Senegal, and Haiti showing an increased incidence of female mortality occurring after administration of HT Edmonston-Zagreb vaccination. We reviewed 9 studies of HT measles vaccines that reported data on mortality. These reports included 4 randomized trials comparing HT vaccine administered to children younger than 9 months with standard-titer (ST) vaccines (10(3.0) to 10(4.0) plaque-forming-units) given at 9 months of age. Five studies from Zaire, Haiti, Senegal, Rwanda, and Zaire had no control group receiving ST vaccine at 9 months of age, but investigators were able to examine the female-to-male mortality ratio within these HT studies. Investigators have hypothesized that HT vaccine had caused immune suppression similar to that of measles infection. The present review suggests first that the HT vaccine itself is unlikely to be the cause because the effect was not found in all studies. Second, the increased mortality started only after 9 to 10 months of age when controls received ST measles vaccine, and HT groups received the "control vaccine." It was not found in the studies that provided another measles vaccine instead of control vaccine. Third, because the HT studies with excess mortality rates showed increased female mortality rates, we need to find environmental or contextual conditions associated with increased female mortality rates in some studies to explain the problem associated with HT measles vaccination.

Background: It has been assumed that measles infection may be associated with persistent immune suppression and long-term excess mortality. However, few community studies of mortality after measles infection have been carried out. We examined long-term mortality for measles cases, sub-clinical measles cases, and uninfected contacts after an epidemic in rural Senegal. Methods: The study was carried out in Niakhar, a rural area of Senegal. Index cases of measles were identified and children less than 7 years of age exposed to measles in the same compound had acute and convalescent blood samples collected. Clinically diagnosed measles cases were serologically confirmed. Children without clinical symptoms were classified as sub-clinical cases if they had a four-fold or greater change in antibody levels between samples collected at exposure and 1 month later and as uninfected if there was no or a two-fold change in antibody levels. Results: There were 31 index cases, and among 184 exposed contacts, 35 (19%) children developed clinical measles. Among contacts that did not develop clinical measles, 45% had sub-clinical infection. Measles cases, sub-clinical cases, and uninfected contacts did not differ with respect to nutritional status. However, uninfected children without clinical symptoms and change in antibody level had higher initial measles specific IgG antibody levels and less intensive exposure to the index case. No index or secondary case of measles died in the acute phase of infection nor did any of the children exposed to measles die in the first 2 months after exposure. Exposed children developing clinical measles had lower age-adjusted mortality over the next 4 years than exposed children who did not develop clinical measles (P

It has been suggested that measles infection mainly kills frail children who are likely to die anyhow of other infections. If that were true, the proportion of frail children should increase after the introduction of measles vaccination and post-measles mortality compared with mortality in uninfected children should increase when the case fatality declines and frail children are no longer dying of measles. The latter deduction was investigated in Niakhar, Senegal, where the measles case fatality has declined markedly. Measles has been studied in Niakhar during 12 years from 1983 to 1994. We compared long-term mortality after measles infection in periods with both high and low case fatality. The acute measles case fatality rate (CFR) declined from 6.5% in 1983–1986 to 1.5% in 1987–1994, an age-adjusted decline of 66% (RR=0.34 (0.19–0.58)). Between 1983–1986 and 1987–1994, mortality in the first year after measles infection declined by 35% (RR=0.65 (0.37–1.16)), the pattern being the same in the second and third year after infection (RR=0.63 (0.33–1.21)). This reduction could not be related to introduction of immunization, treatment of measles with Vitamin A, or prophylactic use of antibiotics. Controlling for age, immunization, and season, the decline in post-measles mortality was similar to the fall in non-measles-related mortality between the two periods (mortality rate ratio=0.72 (0.64–0.80)). Since the mortality decline in survivors of measles was as large as the decline in mortality among uninfected children, reduction in acute measles mortality did not lead to accumulation of frail children. We doubt measles infection ever eliminated mainly weak children; it always killed a broad spectrum of children, most of whom were “fit to survive”. Hence, it seems unlikely that measles vaccination has contributed to the survival of more frail children.

BACKGROUND The measure of efficacy is optimally performed by randomized controlled trials. However, low specificity of the judgement criteria is known to bias toward lower estimation, while low sensitivity increases the required sample size. A common technique for ensuring good specificity without a drop in sensitivity is to use several diagnostic tests in parallel, with each of them being specific. This approach is similar to the more general situation of case-counting from multiple data sources, and this paper explores the application of the capture-recapture method for the analysis of the estimates of efficacy. METHOD An illustration of this application is derived from a study on the efficacy of pertussis vaccines where the outcome was based on > or =21 days of cough confirmed by at least one of three criteria performed independently for each subject: bacteriology, serology, or epidemiological link. Log-linear methods were applied to these data considered as three sources of information. RESULTS The best model considered the three simple effects and an interaction term between bacteriology and epidemiological linkage. Among the 801 children experiencing > or =21 days of cough, it was estimated that 93 cases were missed, leading to a corrected total of 413 confirmed cases. The relative vaccine efficacy estimated from the same model was 1.50 (95% confidence interval: 1.24-1.82), similar to the crude estimate of 1.59 and confirming better protection afforded by one of the two vaccines. CONCLUSION This method allows supporting analysis to interpret primary estimates of vaccine efficacy.

Despite a high coverage with measles vaccines in parts of west Africa, epidemics of measles occur with reduced severity in an increasing proportion of older children who have been vaccinated. We examined the effect of exposure to natural measles on immunity in vaccinated children.Our study was carried out in 1992 during an epidemic of measles in Niakhar, a rural area of Senegal with about 27,000 inhabitants who mostly live in compounds that include several households; within each household people live in different huts. Vaccine coverage in Niakhar was 81% at the time of our study. We measured haemagglutinin-inhibiting antibody at exposure and twice thereafter (after 4-5 weeks and at 6 months) in 36 vaccinated and 87 unvaccinated children. The frequency of measles and subclinical measles--defined as a four-fold or greater rise in antibody titre without clinical signs or symptoms--was related to intensity of exposure according to whether the index case was in the same hut, household, or compound.Clinical measles occurred in 20 (56%) of 36 unvaccinated children and in one (1%) of 87 vaccinated children. Subclinical measles occurred in 39 (45%) of 86 vaccinated children who were exposed to measles and in four (25%) of 16 unvaccinated children. The frequency was inversely related to pre-exposure antibody concentration (p0.001 for trend) and directly related to intensity of exposure (p=0.002 for trend). Antibody concentrations in subclinical cases increased on average by 45-fold and remained raised for at least 6 months.Increased antibody titre after subclinical measles may be common in vaccinated children in West Africa where the intensity of exposure is high. As measles vaccination coverage increases, the circulation of wild measles will decrease, and vaccine-induced antibody is less likely to be boosted. Thus, new epidemics, albeit milder in form, may occur in vaccinated areas which should be recognised in campaigns to eradicate measles.

The anopheline bioecology and the malaria transmission were studied from January to December 1995 in three villages of the sahelian rural area of Niakhar, Senegal. This area of 29000 inhabitants, has been for several decades, a regional observatory for population and health. The three methods used for collecting mosquitoes were the collection at larval stages, the all night human biting collection, and the pyrethrum spray catch in houses during afternoons. The anophelines collected were, by numerical importance: Anopheles arabiensis, An. rufipes, An. gambiae, An. pharoensis, An. funestus and An. coustani. In the An. gambiae complex, An. arabiensis represented 97% of man biting females and 98% of half gravid resting females (difference not significant); the other reminding species of this complex was always An. gambiae. These two species belonging to the An. gambiae complex were responsible for the totality of the transmission. The anthropophilic index, obtained from half gravid indoor resting An. gambiae s.l., was 83%. The annual biting rate of An. gambiae s.l. varied from 512 to 1558 bites per man per night, depending on the villages. Vectors were observed all year long but their densities were low during the dry season. Vector population presented a notable increase due to the rains, with a maximum of about 10 bites per man per night in September or at the beginning of October; during September the biting rate represented 48% of the annual biting rate. The sporozoitic index of An. gambiae s.l., obtained by ELISA revealing the circumsporozoite protein, was 1.6% for human biting females and 1.8% for half-gravid resting females (difference not significant). Plasmodium falciparum was the only plasmodial species observed among infected anophelines. The annual transmission in the vo villages representative of the Niakhar area were 9 and 12 bites of infected anophelines per man, occurring mainly from August to October. In the third village, not representative of the area regarding permanent breeding places, the transmission was 26 bites of infected anopheline per man per year. These results were discussed in the Senegambian and sahelian contexts.

The enzyme-linked immunosorbent assay is widely employed for the serological diagnosis of pertussis. It is generally concluded that a significant increase in specific immunoglobulin G (IgG) or IgA against the pertussis toxin (PT) or against filamentous hemagglutinin (FHA) in paired sera correlates with Bordetella pertussis infection. However, this type of diagnosis of pertussis has mainly been applied to unvaccinated children, with timely sampling of acute- and convalescent-phase sera. In current practice and in epidemiological studies, such criteria are not always fulfilled. The aim of this study was to analyze the significance of decreases in IgG antibody titers against PT and FHA between paired sera observed in suspected cases of pertussis infection. Serological results from paired sera were available for 460 children experiencing at least 8 days of cough. An anti-PT IgG decrease was observed in 25% of the children, more frequently than the anti-FHA IgG decrease. Fourteen percent of the serologic decreases were observed in children with culture-confirmed infection, and 59% of the decreases were observed in children with confirmation criteria according to World Health Organization recommendations. Most of the decreases were observed when serum samples were collected according to a standard recommended schedule. Serologic decreases were observed more frequently among vaccinated children than among unvaccinated children. This difference, which was highly significant ( P < 0.00001), was explained by the different kinetics of the antibody responses between vaccinated and unvaccinated children. The importance of the antibody response for the evaluation of vaccine efficacy, namely a bias toward higher absolute vaccine efficacy when this response is not taken into account, is discussed. This study supports an earlier recommendation that a significant decrease in PT or FHA should be added to the diagnostic criteria for pertussis.

The epidemiology of measles has been investigated in Niakhar, a rural area of Senegal, during two periods, 1983-1986 and 1987-1990. Following a major increase in immunization coverage beginning in 1987, the case fatality ratio for all ages declined fourfold from the first to the second period (relative risk (RR) = 0.24, 95% confidence interval (CI) 0.13-0.46). The measles incidence for children under 10 years of age declined by 69% (95% CI 65-72) and the risk of dying of measles by 91% (95% CI 82-95). Vaccinated children who contracted measles had significantly lower case fatality ratio than unvaccinated children with measles (p = 0.038). Children infected by an immunized case tended to have lower case fatality ratio than those infected by an unimmunized index case (p = 0.104) and immunized index cases generated fewer secondary cases than unimmunized index cases (p < 0.001). Respiratory complications were more common in secondary cases than infected by an index case with respiratory complications than by an index case without such complications (RR = 1.60, 95% CI 1.08-2.37), which suggests that severe cases give rise to further severe cases. As expected, there was a significant increase in the proportion of vaccinated cases in the second period (RR = 1.41, 95% CI 1.00-1.98). Mean age at infection increased from 4 to 7 years between the two periods and the change in age structure accounted for 20% of the decline in case fatality ratio. Measles immunization may contribute to lower mortality directly through reduced incidence and indirectly through increases in age at infection, less severe infection for immunized cases and changes in transmission patterns leading to reduced severity of measles. (Résumé d'auteur)

Finland introduced universal rotavirus (RV) vaccination in September 2009, with exclusive use of the pentavalent human-bovine reassortant RV vaccine RotaTeq® and following a vaccination schedule at 2, 3 and 5 months of age. This study monitored the impact of RV vaccination on hospitalizations due to RV acute gastroenteritis (RVGE). The results following the first 3 RV seasons after implementation of universal RV vaccination are presented.Prospective hospital-based surveillance identified children with acute gastroenteritis admitted to 2 University Hospitals (Tampere and Oulu, Finland), from December 2009 to August 2012. The surveillance covered a population of approximately 173,000 children from the 2 hospitals' catchment areas. Stool samples were taken and analyzed centrally for RV by enzyme-linked immunosorbent assay, with genotyping by reverse transcription polymerase chain reaction. International Classification of Diseases discharge codes were collected retrospectively pre- and postvaccination.During the 3-year prospective surveillance, 127 RVGE episodes were identified. Of these, 117 were in unvaccinated children and 6 were in fully vaccinated children (RotaTeq, n = 3; Rotarix, n = 3). The vaccine effectiveness against hospitalized RVGE for fully vaccinated children was 92.1% [95% confidence interval (CI): 50.0-98.7] among children eligible for the National Immunization Program. When analyzing retrospectively the Tampere and Oulu hospital databases for all children aged16 years, hospitalizations for RVGE had decreased by 78% in the postvaccination period (2009-2012) compared with the prevaccination data (2001-2006).Severe RVGE requiring hospitalization was virtually eliminated in vaccine-eligible children in the 3 years following implementation of universal RotaTeq vaccination in Finland.

Once a vaccine is licensed and introduced in the population, post-licensure studies are required to measure vaccine effectiveness and impact of vaccination programmes on the population at large. However, confusion still prevails around these concepts, making it difficult to discern which effects are measured in such studies and how their findings should be interpreted. We review from the public health evaluation perspective the effects of vaccine-related exposures, describe the methods used to measure them and their assumptions. We distinguish effects due to exposure to individual vaccination from those due to exposure to a vaccination programme, as the latter depends on vaccine coverage, other population factors and includes indirect effects as well. Vaccine (direct) effectiveness is estimated by comparing vaccinated and unvaccinated individuals exposed to the same vaccination programme. The impact of a vaccination programme, defined here as the population prevented fraction when exposure is the programme, is measured by comparing populations with and without a vaccination programme, most commonly the same population before and after vaccination. These designs are based on a number of assumptions for valid inference. In particular, they assume that vaccinees and non-vaccinees do not differ in terms of susceptibility and exposure to the disease or in ascertainment of vaccination and disease status. In pre and post-vaccination design, the population is assumed to have similar baseline transmission, case detection and reporting, risk factors and medical practices in both periods. These principles are frequently violated in post-licensure studies. Potential confounding and biases must be minimized in study design and analyses, or taken into account during result interpretation. It is also essential to define which exposure is evaluated (individual vaccination or vaccination programme) and which effect is measured. This may help decision-makers clarify which type of study is needed and how to interpret the results. (C) 2013 Elsevier Ltd. All rights reserved.

A diphtheria and tetanus toxoid two-component acellular pertussis vaccine (DTaP), consisting of 25 micrograms glutaraldehyde-detoxified pertussis toxin (PT) and 25 micrograms native filamentous hemagglutinin (FHA), was compared with diphtheria and tetanus toxoid whole-cell pertussis vaccine (DTwP) in a randomized, double-blind manner in 286 Senegalese infants inoculated at two, four, and six months of age. In infants receiving DTaP a significantly lower rate of local reactions, crying and fever was observed than in infants receiving DTwP. One month after the third dose, the geometric mean titres for FHA antibodies were higher in the DTaP group, whereas increases in PT antibody titres were higher in the DTwP group. More than 90% of the infants had a fourfold or more increase in antibodies to both PT and FHA with either vaccine. Diphtheria, tetanus, and polio antibody responses were also measured and found to be comparable between the two groups. The results of this pilot study support the implementation of a field trial to compare the protective efficacy of these vaccines against pertussis in the same setting.

To examine whether the reduction in mortality after standard titre measles immunisation in developing countries can be explained simply by the prevention of acute measles and its long term consequences.An analysis of all studies comparing mortality of unimmunised children and children immunised with standard titre measles vaccine in developing countries.10 cohort and two case-control studies from Bangladesh, Benin, Burundi, Guinea-Bissau, Haiti, Senegal, and Zaire.Protective efficacy of standard titre measles immunisation against all cause mortality. Extent to which difference in mortality between immunised and unimmunised children could be explained by prevention of measles disease.Protective efficacy against death after measles immunisation ranged from 30% to 86%. Efficacy was highest in the studies with short follow up and when children were immunised in infancy (range 44-100%). Vaccine efficacy against death was much greater than the proportion of deaths attributed to acute measles disease. In four studies from Guinea-Bissau, Senegal, and Burundi vaccine efficacy against death remained almost unchanged when cases of measles were excluded from the analysis. Diphtheria-tetanus-pertussis and polio vaccinations were not associated with reduction in mortality.These observations suggest that standard titre measles vaccine may confer a beneficial effect which is unrelated to the specific protection against measles disease.Ten cohort and two case-control studies from Bangladesh, Benin, Burundi, Guinea-Bissau, Haiti, Senegal, and Zaire comparing the mortality of nonimmunized children and children immunized with standard titre measles vaccine were analyzed to determine whether the reduction in mortality after standard titre measles immunization can be explained simply by the prevention of acute measles and its long-term consequences. Protective efficacy against death after measles immunization ranged from 30% to 86%. Efficacy was highest in the studies with short follow-up and when children were immunized in infancy. Vaccine efficacy against death was much greater than the proportion of deaths attributed to acute measles disease. In four studies from Guinea-Bissau, Senegal, and Burundi, vaccine efficacy against death remained almost unchanged when cases of measles were excluded from the analysis. Finally, diphtheria-tetanus-pertussis and polio vaccinations were not associated with reduction in mortality. These findings suggest that standard titre measles vaccine may confer a beneficial effect against mortality which is unrelated to the specific protection against measles disease.

In 1986, the government of Congo undertook a structural adjustment programme to cope with the economic crisis. We present the results of a study whose objectives were to assess the evolution of nutritional status of an urban community between 1986 and 1991 and to identify specific groups for which the nutritional status may have worsened.Two cross-sectional surveys were carried out on representative samples of Brazzaville children6 years old: 2295 children were surveyed in 1986 and 2373 in 1991. Anthropometric assessment of nutritional status was performed. For children, weight-for-height and height-for-age indices were used according to WHO recommendations. Wasting and stunting were respectively defined as indices under -2 z-scores. Body mass index of mothers was calculated and risk of chronic energy deficiency (CED) was defined as18.5 kg/m2. Socioeconomic data relative to the households were also collected. Multivariate statistical methods were used to obtain adjusted estimates of nutritional changes in the community.Data analysis led to several converging results: increase in the percentage of low birthweight (10.2% in 1985 versus 18.7% in 1990), increase in the percentage of CED (from 7.9% to 10.5%), and increase in the prevalence of wasting (from 2.9% to 4.2%). By contrast, the overall prevalence of stunting decreased from 13.9% to 11.0%. After statistical adjustment, the factors found to influence the evolution of anthropometric status were: age of child, age of mother, schooling of mother and household characteristics such as number of preschool children, economic level and head of household's occupation.The study enables the negative effects of the economic crisis to be quantified. Body mass index is shown to be sensitive to economic changes. It could be recommended as a possible indicator for monitoring the nutritional status at population level. The results also call for a new impetus in preventive health programmes and the implementation of nutritional surveillance activities.In the face of an economic crisis, the government of Congo in 1986 embarked upon a structural adjustment program. A study was later conducted to assess the evolution of nutritional status in an urban community during 1986-1991, and to identify specific groups for which nutritional status may have worsened. The authors present the results of this study. 2295 children in Brazzaville younger than 6 years of age were surveyed in 1986 and 2373 in 1991. Anthropometric assessment of nutritional status was performed and child weight-for-height and height-for-age indices used according to World Health Organization recommendations. Socioeconomic data relative to the households were also collected. Between 1985 and 1990, the degree of low birth weight increased from 10.2% to 18.7%, chronic energy deficiency from 7.9% to 10.5%, and the prevalence of wasting from 2.9% to 4.2%. The overall prevalence of stunting, however, decreased from 13.9% to 11.0%. After statistical adjustment, child's age, mother's age, mother's schooling, and household characteristics such as the number of preschool children, economic level, and head of household's occupation were found to influence the evolution of anthropometric status. Body mass index has therefore been shown to be sensitive to economic changes and could thus be recommended as a possible indicator for monitoring nutritional status at the population level. Study results also call for a new impetus in preventive health programs and the implementation of nutritional surveillance activities.

Although domestic animals may not be permissive for Plasmodium, they could nevertheless play a role in the epidemiology of malaria by attracting Anopheles away from humans. To investigate interactions between domestic animals and mosquitoes, we assayed immunoglobulin G (IgG) antibodies directed against the salivary proteins of Anopheles gambiae in domestic animals living in Senegalese villages where malaria is endemic. By Western blotting, sera from bovines (n = 6), ovines (n = 36), and caprines (n = 36) did not react with Anopheles whole saliva. In contrast, equine sera recognized proteins in both saliva and salivary gland extracts. Two of the major immunogens (32 and 72 kDa) were also reactive in extracts from other major mosquito genera (Aedes and Culex), but reactions to Anopheles-specific antigens were detected in 12 of 17 horses. These data suggest that horses strongly react to Anopheles bites, and further experiments on horses are warranted to investigate the impact of this domestic animal species on the transmission of human malaria.

International audience; To optimize malaria control, WHO has prioritised the need for new indicators to evaluate the efficacy of malaria vector control strategies. The gSG6-P1 peptide from gSG6 protein of Anopheles gambiae salivary glands was previously designed as a specific salivary sequence of malaria vector species. It was shown that the quantification of human antibody (Ab) responses to Anopheles salivary proteins in general and especially to the gSG6-P1 peptide was a pertinent biomarker of human exposure to Anopheles. The present objective was to validate this indicator in the evaluation of the efficacy of Insecticide Treated Nets (ITNs). A longitudinal evaluation, including parasitological, entomological and immunological assessments, was conducted on children and adults from a malaria-endemic area before and after the introduction of ITNs. Significant decrease of anti-gSG6-P1 IgG response was observed just after the efficient ITNs use. Interestingly, specific IgG Ab level was especially pertinent to evaluate a short-time period of ITNs efficacy and at individual level. However, specific IgG rose back up within four months as correct ITN use waned. IgG responses to one salivary peptide could constitute a reliable biomarker for the evaluation of ITN efficacy, at short- and long-term use, and provide a valuable tool in malaria vector control based on a real measurement of human-vector contact.

Background Intermittent preventive treatment in children (IPTc) is a promising strategy to control malaria morbidity. A significant concern is whether IPTc increases children's susceptibility to subsequent malaria infection by altering their anti-Plasmodium acquired immunity. Methods To investigate this concern, IgG antibody (Ab) responses to Plasmodium falciparum schizont extract were measured in Senegalese children (6 months-5 years old) who had received three rounds of IPTc with artesunate + sulphadoxine-pyrimethamine (or placebo) at monthly intervals eight months earlier. Potential confounding factors, such as asexual malaria parasitaemia and nutritional status were also evaluated. Results Firstly, a bivariate analysis showed that children who had received IPTc had lower anti-Plasmodium IgG Ab levels than the non-treated controls. When epidemiological parameters were incorporated into a multivariate regression, gender, nutritional status and haemoglobin concentration did not have any significant influence. In contrast, parasitaemia, past malaria morbidity and increasing age were strongly associated with a higher specific IgG response. Conclusions The intensity of the contacts with P. falciparum seems to represent the main factor influencing anti-schizont IgG responses. Previous IPTc does not seem to interfere with this parasite-dependent acquired humoral response eight months after the last drug administration.

International audience; For the fight against malaria, the World Health Organization (WHO) has emphasized the need for indicators to evaluate the efficacy of vector-control strategies. This study investigates a potential immunological marker, based on human antibody responses to Anopheles saliva, as a new indicator to evaluate the efficacy of insecticide-treated nets (ITNs). Parasitological, entomological, and immunological assessments were carried out in children and adults from a malaria-endemic region of Angola before and after the introduction of ITNs. Immunoglobulin G (IgG) levels to An. gambiae saliva were positively associated with the intensity of An. gambiae exposure and malaria infection. A significant decrease in the anti-saliva IgG response was observed after the introduction of ITNs, and this was associated with a drop in parasite load. This study represents the first stage in the development of a new indicator to evaluate the efficacy of malaria vector-control strategies, which could apply in other arthropod vector-borne diseases.

Mathematical models may be used to help clarify dynamics of several infectious diseases. Because of the complexity of some models and the high degree of uncertainty in estimating many parameters, the present study proposes a rigorous framework for sensitivity analyses of mathematical models using as example a model to assess varicella and herpes zoster incidence. Its main steps are to assess the uncertainty of the factors to be studied, to evaluate qualitatively and quantitatively the impacts of these factors on model results, and to conduct an univariate and multivariate sensitivity analysis. The application of this technique may have considerable utility in the analysis of a wide variety of complex biological and epidemiological models.

Five growth models are compared using weight data from 95 rural Congolese infants between birth and 13 months of age. The objective is to find the best model in terms of goodness of fit and distribution of parameter estimates. The Infancy component of the Karlberg model, the Count model, and the Kouchi model, which are all three-parameter models, are tested together with the four- and five-parameter versions of the Reed model. The closest fits are obtained using the Reed models, followed by the Karlberg model, while the Count and Kouchi models provide poor fits. The five-parameter Reed model is not superior to the four-parameter version. Examination of mean residuals by age shows a systematic bias in neonatal weight estimation with the three-parameter models. Mean within- and between-individual correlations are especially high for the Kouchi and Reed models. Extreme skewness is observed for some parameters of the Kouchi model and of the five-parameter Reed model. Despite its high degree of collinearity, the four-parameter linear Reed model should be preferred on weight data between birth and 1 year. The I-component of the Karlberg model could be used between ages 2 and 12 months. © 1992 Wiley-Liss, Inc.

In sub-Saharan Africa, malaria and malnutrition are major causes of morbidity and mortality in children less than five years of age. To explore the impact of malnutrition on subsequent susceptibility to malaria, a cohort of 874 rural preschool children in Senegal was followed-up during one malaria transmission season from July through December. Data on nutritional status and Plasmodium falciparum parasitemia were collected at baseline. Malaria morbidity was monitored through weekly home visits. Wasted children (weight-for-height z-score < -2) were at lower risk of having at least one subsequent clinical malaria attack (odds ratio = 0.33; 95% confidence interval = 0.13-0.81, P = 0.02), whereas stunting (height-for-age z-score < -2) or being underweight (weight-for-age z-score < -2) was not associated with clinical malaria. Although non-biological explanations such as overprotection of wasted children by their mothers should be considered, immunomodulation according to nutritional status could explain the lower risk of malaria attack among wasted children.

Background Human populations exposed to low malaria transmission present particular severe risks of malaria morbidity and mortality. In addition, in a context of low-level exposure to Anopheles vector, conventional entomological methods used for sampling Anopheles populations are insufficiently sensitive and probably under-estimate the real risk of malaria transmission. The evaluation of antibody (Ab) responses to arthropod salivary proteins constitutes a novel tool for estimating exposure level to insect bites. In the case of malaria, a recent study has shown that human IgG responses to the gSG6-P1 peptide represented a specific biomarker of exposure to Anopheles gambiae bites. The objective of this study was to investigate if this biomarker can be used to estimate low-level exposure of individuals to Anopheles vector. Methods The IgG Ab level to gSG6-P1 was evaluated at the peak and at the end of the An. gambiae exposure season in children living in Senegalese villages, where the Anopheles density was estimated to be very low by classical entomological trapping but where malaria transmission occurred during the studied season. Results Specific IgG responses to gSG6-P1 were observed in children exposed to very low-level of Anopheles bites. In addition, a significant increase in the specific IgG Ab level was observed during the Anopheles exposure season whereas classical entomological data have reported very few or no Anopheles during the studied period. Furthermore, this biomarker may also be applicable to evaluate the heterogeneity of individual exposure. Conclusion The results strengthen the hypothesis that the evaluation of IgG responses to gSG6-P1 during the season of exposure could reflect the real human contact with anthropophilic Anopheles and suggest that this biomarker of low exposure could be used at the individual level. This promising immuno-epidemiological marker could represent a useful tool to assess the risk to very low exposure to malaria vectors as observed in seasonal, urban, altitude or travellers contexts. In addition, this biomarker could be used for the surveillance survey after applying anti-vector strategy.

Routine weight measurements, recorded on health cards of 95 Congolese infants, were collected during a cross-sectional survey as the children were aged 1 to 5 years. The subjects were divided into two groups according to height-for-age (more or less than – 2 SD of NCHS reference) at the time of the survey. Adjustment of a mathematical function to the infancy weight curves allowed comparison of groups using the means of the function's parameters: The stunted children had been significantly lighter than the healthy group during infancy. Predictive values of estimated weights and quarterly weight gains were assessed by discriminant analysis and cut-off points were computed. The weight gain between 3 and 6 months of age predicted stunting just as well as weight at age 1 year did. Sensitivity and specificity were at 77 % and 74 %, respectively. These results suggest that good prediction of stunting is possible from first-year weight measurements.

International audience; Background: n order to improve malaria control, and under the aegis of WHO recommendations, many efforts are being devoted to developing new tools for identifying geographic areas with high risk of parasite transmission. Evaluation of the human antibody response to arthropod salivary proteins could be an epidemiological indicator of exposure to vector bites, and therefore to risk of pathogen transmission. In the case of malaria, which is transmitted only by anopheline mosquitoes, maximal specificity could be achieved through identification of immunogenic proteins specific to the Anopheles genus. The objective of the present study was to determine whether the IgG response to the Anopheles gambiae gSG6 protein, from its recombinant form to derived synthetic peptides, could be an immunological marker of exposure specific to Anopheles gambiae bites.Methodology/Principal Findings: Specific IgG antibodies to recombinant gSG6 protein were observed in children living in a Senegalese area exposed to malaria. With the objective of optimizing Anopheles specificity and reproducibility, we designed five gSG6-based peptide sequences using a bioinformatic approach, taking into consideration i) their potential antigenic properties and ii) the absence of cross-reactivity with protein sequences of other arthropods/organisms. The specific anti-peptide IgG antibody response was evaluated in exposed children. The five gSG6 peptides showed differing antigenic properties, with gSG6-P1 and gSG6-P2 exhibiting the highest antigenicity. However, a significant increase in the specific IgG response during the rainy season and a positive association between the IgG level and the level of exposure to Anopheles gambiae bites was significant only for gSG6-P1.Conclusions/Significance: This step-by-step approach suggests that gSG6-P1 could be an optimal candidate marker for evaluating exposure to Anopheles gambiae bites. This marker could be employed as a geographic indicator, like remote sensing techniques, for mapping the risk of malaria. It could also represent a direct criterion of efficacy in evaluation of vector control strategies