RESUMEN
Benefit/risk (B/R) assessment methods are increasingly being used by regulators and companies as an important decision-making tool and their outputs as the basis of communication. B/R appraisal of vaccines, as compared with drugs, is different due to their attributes and their use. For example, vaccines are typically given to healthy people, and, for some vaccines, benefits exist both at the population and individual level. For vaccines in particular, factors such as the benefit afforded through herd effects as a function of vaccine coverage and consequently impact the B/R ratio, should also be taken into consideration and parameterized in B/R assessment models. Currently, there is no single agreed methodology for vaccine B/R assessment that can fully capture all these aspects. The conference "Perspectives on Benefit-Risk Decision-making in Vaccinology," held in Annecy (France), addressed these issues and provided recommendations on how to advance the science and practice of B/R assessment of vaccines and vaccination programs.
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Toma de Decisiones , Transmisión de Enfermedad Infecciosa/prevención & control , Evaluación de Medicamentos/métodos , Medición de Riesgo , Vacunas/administración & dosificación , Vacunas/inmunología , Francia , Humanos , Resultado del TratamientoAsunto(s)
Evolución Biológica , Interacciones Huésped-Patógeno , Vacunación , Bacterias/genética , Bacterias/inmunología , Control de Enfermedades Transmisibles , Enfermedades Transmisibles/inmunología , Genética de Población , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Virus/genética , Virus/inmunologíaRESUMEN
OBJECTIVE: To describe levels, monthly variations and trends in weight and arm circumference of non-pregnant lactating women living in the Sahel, characterized by one short yearly rainy season (July-October). METHODS: A mixed unbalanced cross-sectional longitudinal observational study conducted at 3, 5, 7 and 10 months postpartum among 3869 women living in the Sine area in central Senegal who had brought their infants into dispensaries for immunization from January 1990 to February 1997, and 1-5 consecutive children per woman (26 106 visits). RESULTS: Mean weight was 55.7 kg (s.d.: 7.1), but it varied by 2.5-3.9 kg each year, from high means during the dry season (March-May) to low means at the end of the rainy season (September-November). The prevalence of underweight, overweight and obesity (body mass index (BMI)<18.5, 25-29.9 and >30 kg/m(2), respectively) was 7.6% (95% confidence interval: 7.3, 7.9), 6.4% (6.1, 6.7) and 0.4% (0.3, 0.4), but varied strongly by season (P<0.0001 for all). Unlike weight, mean arm increased during the early rains, a peak season of agricultural work (+0.10 cm/month (s.d.: 0.6) from June to August vs -0.35 kg/month (s.d.: 1.1) for weight). BMI and arm circumference were positively associated with age (mean: 20.8 vs 22.2 kg/m(2) and 25.3 vs 27.4 cm, at 20-24 and 40-49 years, respectively, P<0.0001 for both). CONCLUSIONS: Season was a major determinant of the anthropometric status of rural African women. Negative energy balance reduced body weight from the onset of agricultural labour, while arm circumference increased during early rains, probably due to high physical activity.
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Agricultura , Brazo/anatomía & histología , Peso Corporal/fisiología , Metabolismo Energético/fisiología , Lactancia/fisiología , Estaciones del Año , Adaptación Fisiológica/fisiología , Adulto , Factores de Edad , Estudios Transversales , Femenino , Humanos , Lactancia/metabolismo , Estudios Longitudinales , Persona de Mediana Edad , Obesidad/epidemiología , Sobrepeso/epidemiología , Periodo Posparto , Prevalencia , Salud Rural , Delgadez/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: 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. DESIGN: Controlled randomised population-based trial. SETTING: Six villages in the Sine area of Senegal, West Africa. SUBJECTS: Healthy breastfed infants and their mothers, 68 controls and 66 supplemented infants at randomization. INTERVENTION: 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. RESULTS: 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). CONCLUSIONS: 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. SPONSORSHIP: This study was supported by a grant from the French Ministry of Research (Grant 92L0623).
Asunto(s)
Lactancia Materna/estadística & datos numéricos , Lactancia/fisiología , Bienestar Materno , Destete , Pérdida de Peso/fisiología , Adulto , Alimentación con Biberón , Femenino , Humanos , Lactante , Alimentos Infantiles , Fenómenos Fisiológicos Nutricionales del Lactante , Fenómenos Fisiologicos Nutricionales Maternos , Embarazo , Índice de Embarazo , Modelos de Riesgos Proporcionales , Senegal , Factores de TiempoRESUMEN
In Senegal, the Expanded Programme of Immunization started by 1986 as a routine programme targeting 7 diseases: tuberculosis, tetanus, diphtheria, pertussis, poliomyelitis, measles and recently yellow fever Immunization against hepatitis B and Haemophilus influenzae b are proposed since 2005, but not implemented yet. In addition, there are mass immunization campaigns, such as National Immunization Day organized every year since 1999 against poliomyelitis and, in case of outbreak, against meningitis or yellow fever. In a 30,000 inhabitants rural study zone, vaccine contacts of children under 15 years of age are updated regularly several times a year since 1984. We also performed yearly cross sectional surveys from 1999 to estimate vaccine coverage in children of 24 months of age. Immunization status was assessed by vaccination cards presented by the children's parents and registers of health centres. We compared the results from both longitudinal and cross sectional surveys, which showed some differences. The last method seemed to indicate higher immunization rates. The vaccine coverage was slightly but not significantly higher in the study zone compared to the general vaccine coverage in Senegal, excepted for measles immunization for which the coverage was significantly lower in Niakhar. However results showed that interventions of all types lead to a high vaccine coverage (up to 80%) but are not sustainable. In the intervals, vaccine coverage decreased dramatically (below 40%), due mainly to irregular supply of antigens and poor accessibility of health facilities. Other factors are mentioned.
Asunto(s)
Vacunación/estadística & datos numéricos , Promoción de la Salud/estadística & datos numéricos , Humanos , Población Rural , Senegal , Factores de TiempoRESUMEN
OBJECTIVE: To study the effect of vaccination on mortality before 2 years of age in a developing country. DESIGN: Prospective cohort study. SETTING: Rural communities in Burkina Faso. PARTICIPANTS: 9085 children born in the study area between 1985 and 1993. MAIN OUTCOME MEASURE: Child death rate. RESULTS: Mortality before 2 years of age was lower in children who had been vaccinated: those vaccinated with BCG only had significantly lower mortality (risk ratio for vaccinated v unvaccinated children 0.37, 95% confidence interval 0.29 to 0.48) as did those vaccinated with diphtheria, tetanus, and pertussis only (0.24, 0.13 to 0.43). The second dose of diphtheria, tetanus, and pertussis was not associated with lower mortality (0.80, 0.58 to 1.12). CONCLUSION: Vaccination with diphtheria, tetanus, and pertussis as well as BCG is associated with better survival of children up to 2 years of age.
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Vacuna BCG , Vacuna contra Difteria, Tétanos y Tos Ferina , Vacunación/mortalidad , Burkina Faso/epidemiología , Estudios de Cohortes , Femenino , Humanos , Lactante , Mortalidad Infantil , Recién Nacido , Masculino , Estudios Prospectivos , Factores de Riesgo , Salud Rural , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To evaluate body composition changes using bioelectrical impedance analysis and skinfold thickness measurements in infants from tropical areas who become stunted between 4-18 months of age. DESIGN AND MEASUREMENTS: Follow-up study. Extracellular water to total body water ratio index (length(2)/resistance at low to high frequency), peripheral fat (tricipital and subscapular skinfold thickness), and length-for-age index were studied at 4 and 18 months of age. SETTINGS: Low-income areas in four tropical regions (Congo, Senegal, Bolivia and New Caledonia). SUBJECTS: Infants were included in the analysis provided they were neither stunted nor wasted at 4 months. Two groups of infants were compared, those that were stunted at 18 months (n=61) or not (n=170). RESULTS: The extracellular water to total body water ratio index and the sum of skinfold thickness measurements were similar in the two groups at 4 months, and only the extracellular water to total body water ratio index was significantly different at 18 months. When no stunting appeared between 4 and 18 months, the change in the extracellular water to total body water ratio index was not linked with variations in length-for-age, and presented the expected pattern of variation in body water compartments. When stunting occurred, variation in length-for-age was related to significant changes in the extracellular water to total body water ratio index, the biggest increase in the proportion of extracellular water being found in the most stunted infants. Variations in the sum of the two skinfold thickness measurements presented the expected pattern for the 4-18 months growth and did not differ between the two groups. CONCLUSIONS: Multifrequency resistances suggested that stunting was associated with a lack of the expansion of the intracellular compartment that is expected during normal growth of cell mass, together with preserved fat mass. SPONSORSHIPS: Supported by grant 92L0623 from the French Ministry of Research, and by Institut de Recherche pour le Développement (IRD).
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Agua Corporal/fisiología , Trastornos del Crecimiento/fisiopatología , Tejido Adiposo/fisiología , África , Factores de Edad , Estatura/fisiología , Peso Corporal/fisiología , Bolivia , Impedancia Eléctrica , Líquido Extracelular/fisiología , Estudios de Seguimiento , Humanos , Lactante , Nueva Caledonia , Pobreza , Grosor de los Pliegues CutáneosRESUMEN
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.
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Sarampión/mortalidad , Modelos Biológicos , Niño , Preescolar , Factores Epidemiológicos , Humanos , Lactante , Sarampión/prevención & control , Vacuna Antisarampión/farmacología , Aptitud Física , Senegal/epidemiología , Factores de TiempoRESUMEN
BACKGROUND: In many developing countries, breastfed children have a lower nutritional status than those weaned from 12 months of age. Reverse causality, that is, earlier weaning of healthy and well-nourished children, is a possible explanation. METHODS: Maternal reasons for early and late weaning were investigated in a cohort of 485 rural Senegalese children using structured interviews during two rounds at the ages of 18--28 and 23--33 months, respectively. Length, weight and height were assessed, and dates of weaning were monitored. RESULTS: The mean duration of breastfeeding was 24.1 months (quartiles 21.9 and 26.3). Two-thirds of mothers of breastfed children under 2 stated that they would wean at the age of 2, while for breastfed children aged 2 years, a 'tall and strong' child was the most prevalent criterion. The main reasons for weaning prior to 2 years (N = 244) were that the child ate well from the family plate (60%), that the child was 'tall and strong' (46%) and maternal pregnancy (35%). The main reasons for weaning later than the age of 2 were: a 'little, weak' child (33%), food shortage (25%), illness of the child (24%) and refusal of family food (14%, N = 120). Children breastfed above the age of 2 because they were 'small and weak' had lower mean height-for-age and a greater prevalence of stunting than children breastfed late for other reasons (P < 0.0001). CONCLUSION: The habit of postponing weaning of stunted children very likely explains why breastfed children have lower height-for-age than weaned children in this setting.
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Apetito , Estatura , Peso Corporal , Países en Desarrollo , Trastornos del Crecimiento/epidemiología , Destete , Factores de Edad , Análisis de Varianza , Lactancia Materna , Distribución de Chi-Cuadrado , Preescolar , Toma de Decisiones , Femenino , Humanos , Lactante , Entrevistas como Asunto , Estado Nutricional , Factores de Riesgo , Salud Rural , Senegal/epidemiología , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Prolonged breast-feeding is frequently associated with malnutrition in less-developed countries, even after adjustment for socioeconomic confounders. However, in rural Senegal, breast-feeding is prolonged when the child is stunted. OBJECTIVE: We aimed to test whether the lower height-for-age of children weaned late is explained by their height before weaning or whether prolonged breast-feeding is associated with impaired growth. DESIGN: A cohort of 443 Senegalese children recruited from dispensaries at 2 mo of age were visited in their homes at 6-mo intervals when they were approximately 1.5 to 3 y of age. Weight, length, arm circumference, and triceps skinfold thickness were measured. Six-month increments were analyzed in relation to breast-feeding (breast-fed compared with weaned children or breast-feeding duration), season, and maternal housing with use of multiple linear regression. RESULTS: The mean duration of breast-feeding was 24.1 mo (quartiles 1 and 3: 21.9 and 26.4). Height-for-age at the age of 3 y was negatively associated with age at weaning (P < 0.01), but this association disappeared after adjustment for height-for-age in infancy. Length increments were significantly greater in both the second and third years of life in children breast-fed for longer durations (P < 0.05) and tended to be greater in breast-fed than in weaned children in the second year of life (P = 0.05). In the third year of life, breast-fed children had greater length increments than did weaned children in the subgroup with poor housing (P for interaction < 0.05). Growth in weight did not differ significantly according to breast-feeding. CONCLUSION: Prolonged breast-feeding improved linear growth, and the negative relation between height-for-age and duration of breast-feeding was due to reverse causality.
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Estatura , Peso Corporal , Lactancia Materna , Análisis de Varianza , Tos/epidemiología , Países en Desarrollo , Diarrea/epidemiología , Dieta , Fiebre/epidemiología , Trastornos del Crecimiento/epidemiología , Vivienda , Humanos , Lactante , Estudios Longitudinales , Prevalencia , Estudios Prospectivos , Población Rural , Estaciones del Año , Senegal/epidemiología , Grosor de los Pliegues Cutáneos , Factores Socioeconómicos , Factores de Tiempo , DesteteRESUMEN
There are a number of reasons why climate, in certain physical and social environments, could have an impact on the epidemiology of malaria. Events, such as floods or drought, are related to the number of malaria cases and deaths, both seasonally and interannually. At a smaller scale, this study analyses the relation between climate variability and the variability in the number of deaths attributable to malaria in Niakhar, Senegal. The Niakhar area has a population of 30,000 and has been under demographic surveillance system since 1984. The rainfall in this region is highly seasonal, with a rainfall maximum in August and almost no rain between October/November and May/June. In addition to this seasonal cycle, rainfall also varies greatly from year to year (interannual variation). Over the 13 years, there were 661 deaths attributed to malaria with a marked interannual variability (range from 23 to 100, with a median of 43). There was also a strong seasonality in mortality, with nearly all deaths (89.1%) occurring between August and December. The number of deaths peaks in October, two months after the rainfall peak. Standardised monthly values were calculated for each climatic series (rainfall, relative humidity, temperature) as well as standardised five-month and monthly values of the number of deaths attributed to malaria between August and December. Correlation coefficients were calculated between these standardised values. The correlation between the variability in August rainfall and the variability in the number of deaths attributed to malaria between August and December was positive and statistically significant (r = +0.61, p = 0.02). In addition, highly significant cross-correlations were found between monthly rainfall series and monthly mortality series at one- and two-month lag (r = + 0.43, p = 0.0004 for one-month lag; r = + 0.26, p = 0.03 for two-month lag). This correlation is somewhat lower than the correlation of August rainfall alone with August to December mortality, but the result adds confidence to the signal given the increased degrees of freedom in the analysis. Similar, but slightly weaker, results were found when precipitation data were replaced with surface humidity data. Results with temperature were less clear; while temperature could in some circumstances have a direct impact on malaria, in this case here it is possible that the weak negative correlation between malaria deaths and temperature arises mainly because precipitation is physically connected to both the indices, correlating positively with malaria and negatively with temperature. The availability of a continuous demographic and medical survey since 1984 in a region of highly variable rainfall has created a rare opportunity to analyse with some confidence a climate versus malaria relationship. The findings are consistent with our understanding of the proposed link between rainfall and conditions for the reproduction of the malaria vector, leading to a lag time (here of one to two months) between anomalies of rainfall and deaths attributable to malaria. These results may have practical implications in Sub-Saharan regions marked by a great seasonal and interannual variability in rainfall by providing a simple tool to forecast the impact of climate variability on malaria mortality.
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Causas de Muerte/tendencias , Clima , Malaria Falciparum/mortalidad , Estaciones del Año , Tiempo (Meteorología) , Animales , Anopheles/parasitología , Anopheles/fisiología , Humanos , Insectos Vectores/parasitología , Insectos Vectores/fisiología , Malaria Falciparum/transmisión , Mortalidad/tendencias , Vigilancia de la Población , Senegal/epidemiologíaRESUMEN
BACKGROUND: In spite of an improving trend, childhood mortality in rural sub-Saharan Africa remains high and has recently risen in some countries. The factors associated with the long-term decline in childhood mortality are poorly known, due to a lack of data. METHODS: A Senegalese rural population has been under demographic surveillance since 1963. Infant and under-5 mortality rates were calculated for different periods to generate a long-term trend in childhood mortality. Evolution of age and seasonal patterns of mortality were observed. FINDINGS: During the observation period (1963-1999), infant and under-5 mortality rates decreased from 223 per thousand to 80 per thousand and 485 per thousand to 213 per thousand , respectively, with a constant annual rate of decline in the probability of dying since the 1960s (-3.7% and -3.1%, respectively). The age pattern of the under-5 mortality changed drastically, with a large decrease in the death rate between 6 and 24 months of age (from 321 per thousand to 87 per thousand ). This change took place during the 1970s. The seasonal variation, characterized by a greater proportion of deaths during the rainy season, was very marked during the 1960s, then decreased during the 1980s but it has tended to increase again in the 1990s, particularly among children 1-4 years old. CONCLUSION: This study confirms the long-term trend of decrease in child mortality in rural West Africa. Historical knowledge on healthcare developments suggests that immunizations have contributed to the decrease and the change in the age pattern. The re-emergence of malaria seems the most likely explanation for the recent rebound in seasonal variation. Attention to immunization and malaria should continue to be a priority.
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Mortalidad Infantil/tendencias , Población Rural , Distribución por Edad , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Vigilancia de la Población , Probabilidad , Análisis de Regresión , Factores de Riesgo , Estaciones del Año , Senegal/epidemiologíaAsunto(s)
Lactancia Materna , Crecimiento/fisiología , Estado Nutricional , Antropometría , Causalidad , Preescolar , Suplementos Dietéticos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Morbilidad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Salud Rural , Estaciones del Año , Senegal , DesteteRESUMEN
A possible genetic selective pressure related to the long-term use of vaccines has been the object of recent theoretical thought and publications. For more than thirty years, an effective vaccine has been in use against whooping cough on a wide scale basis in several countries. Thus, the Bordetella pertussis model may contribute to the analysis of an evolutionary risk linked to the vaccine. To maintain and improve the control of whooping cough, better vaccination coverage must be achieved in countries where prevalence is low. In countries where high vaccination coverage has been achieved over a long period, a trend toward the resurgence of the disease has been observed. Efforts are therefore now being directed toward primary vaccination and boosters. These two targets require new vaccines with fewer side effects. Outbreaks in highly vaccinated populations have been reported, raising the issues of vaccine efficacy, of the long-term effect of vaccines on the transmission of the disease, and of genetic selective pressure. Time trend modifications of circulating strains related to vaccination practices and vaccine types have been observed and are compatible with a selective pressure of the vaccine on related pathogens. However, evidence for a causal relation is lacking. In order to monitor and understand the various effects the vaccine may be having on the effectiveness of immunisation against whooping cough, further surveillance is needed, integrating a standardised characterisation of circulating strains and vaccines by way of a space-time sampling model.
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Evolución Biológica , Bordetella pertussis/genética , Vacuna contra la Tos Ferina , Selección Genética , Factores de Riesgo , Tos Ferina/epidemiología , Tos Ferina/prevención & controlRESUMEN
Following a study in Senegal (1990-1995) in which the relative efficacy of a diphtheria-tetanus-acellular pertussis vaccine (DTaP) was compared with that of a diphtheria-tetanus-whole-cell pertussis vaccine in children given a simultaneous injection of Bacille Calmette-Guérin (BCG) vaccine, this subsequent study was conducted to evaluate the possible adjuvant effect of the BCG vaccine on acellular pertussis vaccine components. A second objective was to compare the immunogenicity of these components when administered in accordance with a 2-4-6-month (spaced) schedule or an accelerated 2-3-4-month schedule. In all, 390 healthy Senegalese infants were randomly divided into three groups of 130 infants. Antibodies to acellular pertussis components were measured in serum samples obtained within 2 days of the first DTaP dose and 1 month after the third dose. BCG vaccine, given simultaneously with the DTaP vaccine, did not influence the immunogenicity of the acellular pertussis vaccine components when compared with separate administration of the two vaccines. Infants immunised according to a 2-4-6-month schedule had a significantly higher immune response than those immunised according to a 2-3-4-month schedule with respect to the response to pertussis toxoid assessed by seroneutralisation on Chinese hamster ovary cells (P<0.0001). These results suggest that BCG and DTaP vaccines can be given simultaneously without interference or enhancement and that more optimal immunogenicity is achieved with an extended than with an accelerated schedule.
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Anticuerpos Antibacterianos/biosíntesis , Vacuna BCG/inmunología , Bordetella pertussis/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacuna BCG/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular , Humanos , Esquemas de Inmunización , Lactante , Malaria/inmunología , Senegal , Toxoides/inmunologíaRESUMEN
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.
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Vacuna contra la Tos Ferina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Proyectos de Investigación , Tos Ferina/diagnóstico , Adolescente , Niño , Preescolar , Humanos , Incidencia , Lactante , Funciones de Verosimilitud , Modelos Lineales , Senegal/epidemiología , Sensibilidad y Especificidad , Tos Ferina/epidemiología , Tos Ferina/prevención & controlRESUMEN
BACKGROUND: Increases in measles antibodies without rash-illnesses have been documented in previously vaccinated children exposed to measles cases. The phenomenon has been incompletely evaluated in young unvaccinated infants with immunity of maternal origin. METHODS: Monthly cohorts of newborns were prospectively randomized to vaccine and placebo control groups during a trial of high-titre vaccines in Niakhar, Senegal. Measles antibodies were assayed in blood samples of enrolled children collected at 5 months old, when controls received a placebo injection, and at 10 months, when the placebo group was given measles vaccine. Intensive prospective surveillance for measles was conducted throughout the trial. RESULTS: One-fifth (n = 53) of the placebo controls seroconverted, with known exposure to a measles case in only three of them. None of the seroconverters developed a measles-like rash. Sixteen-fold or greater increases in titres were noted in about one-quarter of them. Compared with placebo controls who did not seroconvert, seroconverters were more likely to have had exposure to a measles case and to travel, more likely to be boys than girls, and had significantly lower baseline antibody titres. Measles was endemic in the study area throughout the trial. Seroconversions did not adversely effect subsequent nutritional indices or mortality. CONCLUSIONS: Although laboratory errors and inadvertent injection of vaccine rather than placebo may have played some role, they do not fully explain the above observations, which are consistent with subclinical measles in the seroconverters. The possible role of subclinical measles in occult transmission, its potential effect on the type and duration of subsequent immunity, and its impact on response to primary vaccination need to be determined.
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Enfermedades Endémicas/prevención & control , Vacuna Antisarampión , Sarampión/inmunología , Análisis de Varianza , Anticuerpos Antivirales/sangre , Femenino , Humanos , Lactante , Modelos Logísticos , Masculino , Sarampión/epidemiología , Sarampión/prevención & control , Oportunidad Relativa , Estudios Prospectivos , Senegal/epidemiologíaRESUMEN
Patterns of measles transmission at school and at home were studied in 1995 in a rural area of Senegal with a high level of vaccination coverage. Among 209 case children with a median age of 8 years, there were no deaths, although the case fatality ratio has previously been 6-7% in this area. Forty percent of the case children had been vaccinated against measles; the proportion of vaccinated children was higher among secondary cases (47%) than among index cases (33%) (prevalence ratio = 1.36, 95% confidence interval (CI) 1.04-1.76). Vaccinated index cases may have been less infectious than unvaccinated index cases, since they produced fewer clinical cases among exposed children (relative risk = 0.55, 95% CI 0.29-1.04). The secondary attack rate was lower in the schools than in the homes (relative risk = 0.31, 95% CI 0.20-0.49). The school outbreaks were protracted, with 4-5 generations of cases being seen in the two larger schools. Vaccine efficacy was found to be 57% (95% CI -23 to 85) in the schools and 74% (95% CI 62-82) in the residential compounds. Measles infection resulted in a mean of 3.8 days of absenteeism per case, though this did not appear to have an impact on the children's grades. Among the index cases, 56% of children were probably infected by neighbors in the community, and 7% were probably infected at health centers, 13% outside the community, and 24% in one of the three schools which had outbreaks during the epidemic. However, most of the school-related cases occurred at the beginning and therefore contributed to the general propagation of the epidemic. To prevent school outbreaks, it may be necessary to require vaccination prior to school entry and to revaccinate children in individual schools upon detection of cases of measles. Multidose measles vaccination schedules will be necessary to control measles in developing countries.
Asunto(s)
Países en Desarrollo , Brotes de Enfermedades , Sarampión/transmisión , Población Rural , Instituciones Académicas , Absentismo , Adolescente , Niño , Preescolar , Infecciones Comunitarias Adquiridas/mortalidad , Infecciones Comunitarias Adquiridas/prevención & control , Infecciones Comunitarias Adquiridas/transmisión , Infección Hospitalaria/mortalidad , Infección Hospitalaria/prevención & control , Infección Hospitalaria/transmisión , Brotes de Enfermedades/prevención & control , Femenino , Humanos , Programas de Inmunización , Esquemas de Inmunización , Lactante , Masculino , Sarampión/mortalidad , Sarampión/prevención & control , Vacuna Antisarampión/administración & dosificación , Vigilancia de la Población , Riesgo , Senegal , Tasa de SupervivenciaRESUMEN
PIP: Strebel et al. misinterpreted the authors' paper on the role of schools in measles transmission. As Strebel et al. noted, the main reason for the outbreak was low vaccine coverage among children aged 5-14 years, together with a marked reduction in the incidence of measles over the past 10 years. Because of the high measles vaccine coverage in younger age groups, many children in Niakhar have gone through their first 5 years of life without being infected with the measles virus. The waning of vaccine-induced immunity has played a role. Strebel et al. believe that there is no indication of waning immunity in the authors' paper and that there is a downward bias in vaccine efficacy due to faulty methodology. Their argument, however, misses the point. The children's ages at vaccination with standard vaccine were completely different in those age groups, with the median age being 295 days for those under age 5 years and 1017 days for those aged 10-14 years. Whether waning immunity will translate into declining vaccine efficacy with age depends upon whether misclassification of vaccination status and measles history is the same in all age groups. Other observations support the existence of waning immunity. The phenomenon of waning vaccine-induced immunity needs to be examined for measles and other vaccine-preventable diseases.^ieng
Asunto(s)
Brotes de Enfermedades , Vacuna Antisarampión/inmunología , Sarampión/inmunología , Adolescente , Anticuerpos Antivirales/sangre , Niño , Preescolar , Brotes de Enfermedades/prevención & control , Femenino , Humanos , Esquemas de Inmunización , Lactante , Masculino , Sarampión/prevención & control , Sarampión/transmisión , Vacuna Antisarampión/administración & dosificación , Virus del Sarampión/inmunología , Instituciones Académicas , Senegal , Insuficiencia del TratamientoRESUMEN
BACKGROUND: 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. METHODS: 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. FINDINGS: 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 (p<0.001 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. INTERPRETATION: 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.