Seasonal variations and trends in weight and arm circumference of non-pregnant rural Senegalese women, 1990-1997.

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.

Early short-term infant food supplementation, maternal weight loss and duration of breast-feeding: a randomised controlled trial in rural Senegal.

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).

[Analysis of evolution of vaccine coverage in Niakhar, a rural area of Senegal, between 1984 and 2003]. / Analyse de l'evolution de la couverture vaccinale a Niakhar, région rurale du Sénégal, entre 1984 et 2003.

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.

Perspectives on benefit-risk decision-making in vaccinology: Conference report.

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.

Breast-feeding is associated with improved growth in length, but not weight, in rural Senegalese toddlers.

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.

Effect of early, short-term supplementation on weight and linear growth of 4-7-mo-old infants in developing countries: a four-country randomized trial.

The effect of supplementation on growth was tested by means of four similar controlled randomized trials in the Congo (n = 120), Senegal (n = 110), Bolivia (n = 127), and New Caledonia (n = 90). Four-month-old infants were randomly allocated to supplement or control groups. A cereal-based precooked porridge was offered twice daily for 3 mo and consumption was monitored. Both groups were free to eat local food. At 7 mo of age, all infants were still breast-fed in the Congo, Senegal, and Bolivia compared with 47% in New Caledonia. Mean daily consumption of the supplement varied among countries (558-790 kJ/d). Mean length at 4 mo was lowest in Bolivia, higher in Senegal and the Congo, and near the National Center for Health Statistics reference in New Caledonia. The mean 4-7 mo length increment was 0.48 cm higher for supplemented than for control infants in Senegal (P < 0.05), whereas weight increments did not differ. No significant effect was found in the other countries.

PIP: Findings from this study of the link between nutritional supplementation during breast feeding and infant growth disagree with earlier studies. The effect of nutritional supplementation on growth in length was only modest, but significant only in Senegal and not significant in the Congo, Bolivia, and New Caledonia. It is hypothesized that food supplementation during the 4-7 month period would have a positive effect on linear growth. This study included four controlled randomized trials among 120 infants in the Congo, 110 infants in Senegal, 127 infants in Bolivia, and 90 infants in New Caledonia. The infants were 4 months old when placed in the supplement or control groups. Supplementation included the addition of a cereal-based precooked porridge twice daily for 3 months. Both groups continued to eat local foods. Breast feeding patterns were different in New Caledonia, where only 47% of infants were still breast fed at 7 months of age. Mean daily supplementation varied among countries, from 558 to 790 kJ/day. Mean length was lowest in Bolivia, higher in Senegal and the Congo, and close to the US National Center for Health Statistics reference measures in New Caledonia. The study was conducted in rural parts of Senegal and New Caledonia and periurban parts of Bolivia and the Congo. Supplementation was supervised by field workers. The samples included infants with a length-for-age score of -2.5 or higher and a weight-for-length Z score of -2 or higher at 4 months. Anthropometric measurements were taken at 4 months and 4, 8, and 13 weeks later (at 4.9, 5.8, and 7.0 months of age). 24-hour food recalls were collected monthly for consumption of breast milk, special local infant food, commercial "western" baby food, milk substitutes, family food, water, and other than milk liquids.

Serologic status and measles attack rates among vaccinated and unvaccinated children in rural Senegal.

During a measles vaccine trial in a rural area of Senegal, antibody status was examined within 10 days of exposure for 228 previously vaccinated and 313 unvaccinated children more than 12 months old who were exposed to measles at home. Thirty-six percent of the children developed clinical measles, the clinical diagnosis being confirmed for 135 of the 137 children from whom 2 blood samples were collected. Vaccine efficacy was 90% (95% confidence interval, 83 to 94%). The hemagglutinin-inhibiting antibodies (HI) or plaque neutralizing antibodies (PN) assays were equally efficient in predicting susceptibility and protection against measles. Vaccinated children who had no detectable HI or PN antibodies at exposure had significant protection against measles compared with seronegative unvaccinated children (HI vaccine efficacy, 49% (95% confidence interval, 21 to 68%); PN vaccine efficacy, 43% (95% confidence interval, 12 to 62%)). The attack rate was high for children with a titer of 40 to 125 mIU) 67% (4 of 6) of those with a positive hemagglutinin-inhibiting antibody test and 36% (13 of 36) of those with a positive PN test developed measles. Attack rates among children with HI or PN titers above 125 mIU were 2% (6 of 295) and 3% (7 of 258), respectively. Because titers of < or = 120 mIU have been found to offer little protection in another study, this antibody level may be the best screening value for assessing susceptibility and protection against measles. However, it should be noted that many seronegative vaccinated children are protected against measles infection.

Increased long term mortality associated with rash after early measles vaccination in rural Senegal.

OBJECTIVES: To examine whether clinical symptoms, including rash, were more common after measles immunization compared with placebo and to study the association between postvaccination symptoms and later mortality. DESIGN: Examination of side effects in the 3 weeks after immunization in a trial of high titer and standard titer measles vaccines. PATIENTS: Two hundred twenty-four children randomly selected to be included in the surveillance for diarrhea, fever and rash. RESULTS: There was no difference in fever and diarrhea between recipients of high titer vaccines and recipients of placebo. However, high titer recipients tended to have more measles-like rashes than placebo recipients [relative risk, 2.12 (range, 0.90 to 5.03)]. Among recipients of high titer vaccines, children who presented a rash had higher mortality in the following 5 to 7 years than those who did not develop rash [mortality rate ratio, 3.85 (range, 1.52 to 9.79)]. High titer recipients without a rash had the same mortality as children in the placebo group who were given standard doses of measles vaccine at 10 months of age [mortality rate, 0.76 (range, 0.35 to 1.62)]. CONCLUSIONS: These observations suggest that in this particular study, rash after high titer measles vaccine may identify children who received a particularly high dose of vaccine or children with more severe and persistent postvaccination immunosuppression. Whether high titer vaccine is more likely than standard titer measles vaccine to provoke such reaction is not known, given that we did not compare side effects after different titers of measles vaccine. Future trials of live measles vaccine should monitor the development of rash.

Poor serologic responses five to seven years after immunization with high and standard titer measles vaccines.

BACKGROUND: Few data exist on the persistence of measles antibodies after vaccination of West African infants. Therefore we examined measles antibody titers 5 to 7 years after children in rural Senegal had received high titer Edmonston-Zagreb (EZ-HT), high titer Schwarz (SW-HT) or standard titer Schwarz (SW-STD) measles vaccines in infancy. METHODS: Children had received either high titer vaccines at 5 months of age or standard titer at 10 months of age. Finger prick blood samples were tested for measles antibody 5 to 7 years later by the hemagglutinin inhibition test. RESULTS: Persistence of antibody after high titer vaccines was poor with the result that 39 and 50% of the EZ-HT and the SW-HT groups had low titers of hemagglutinin inhibition measles antibodies (< or =125 mIU/ml). Nineteen percent of the children in the SW-STD group had low titers which is a lower prevalence than in the high titer groups [relative risk (95% confidence intervals), 0.05 (0.28 to 0.88) vs. EZ-HT; relative risk, 0.38 (0.22 to 0.66) vs. SW-HT]. Geometric mean (95% confidence interval) antibody titers in children with detectable values were 616 (435 to 871) in the EZ-HT, 1106 (616 to 1866) in the SW-HT and 1271 (871 to 1741) mIU/ml in the SW-STD groups, respectively. Multivariant regression analysis showed that mean titers were 2.00 (1.03 to 3.89) times higher for children with low prevaccination antibody titers (< or =125 mIU/ml) and 3.06 (1.90 to 4.94) times higher if blood was collected in the rainy season. INTERPRETATION: Given the rapid decline in antibody titers over a 5- to 6-year period in an area where measles vaccine coverage was high, it seems likely that multiple dose immunization schedules will be needed in the future to maintain protective antibody concentrations (>125 mIU/ml) in West Africa. The role of subclinical boosting by exposure to natural measles and the possible role of malaria, which increases immunoglobulin turnover, in influencing long term antibody persistence after vaccination deserve further investigation.

Capture-recapture method for estimating misclassification errors: application to the measurement of vaccine efficacy in randomized controlled trials.

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.

Mothers prolong breastfeeding of undernourished children in rural Senegal.

BACKGROUND: Breastfeeding, when prolonged beyond infancy, is a risk factor for low nutritional status in most cross-sectional samples from less developed countries. Therefore, it has been suggested that prolonged breastfeeding impairs growth. To test whether, on the contrary, breastfeeding is prolonged because the child is already undernourished, nutritional status prior to weaning was compared according to age at weaning. METHODS: Precise dates of birth and weaning were collected weekly through continuous demographic surveillance in a rural area of Senegal. Weight and length at 9-10 months were measured during vaccination sessions (coverage: 78%) from 1989 to 1996. Eight infants weaned before 9 months were excluded, and the duration of breastfeeding of the remaining 4515 children was compared according to nutritional status at 9-10 months by survival analysis. RESULTS: Length-for-age during infancy was associated with duration of breastfeeding: the median duration was 25.0 months for z-scores <-2, 24.1 months for z-scores -2 to -1, 23.4 months for z-scores -1 to 0 and 22.7 months for z-scores >0 (P for trend <0.0001). Weight-for-length during infancy was also associated with duration of breastfeeding (P for trend <0.0001), though the differences among groups were smaller. The relationships remained at the same significance levels after adjustment for season of birth, mother's age, parity, height, occupation and education. CONCLUSION: Duration of breastfeeding is not determined by characteristics of the mothers only. Women prolong breastfeeding for undernourished children and reduce the duration for well-nourished children, probably because they are aware of the mortality risk following weaning.

PIP: Several cross-sectional studies conducted in developing countries have indicated that prolonged breast feeding has a detrimental effect on child growth. It is possible, however, that breast feeding is prolonged in an attempt to correct undernutrition. This possibility was assessed through reference to demographic surveillance data on 4515 infants conducted in rural Senegal in 1989-96. Weaning data were collected weekly and weight and length were measured during vaccination sessions at 9-10 months of age. The prevalences of stunting and wasting were 13.7% and 11.6%, respectively. The median duration of breast feeding was 25.0 months for length-for-age z-scores less than -2, 24.1 months for z-scores from -1 to 0, and 22.7 months for z-scores above 0 (p 0.0001). At 24 months, the probability of still being breast-fed was 70.7% for children with a length-for-age of less than -2 z-scores and 37.5% for those who had a length-for-age above 0 z-score. Weight-for-length was also significantly associated with breast-feeding duration, although the differences among groups were smaller. These associations retained significance after adjustment for season of birth, parity, and maternal age, height, occupation, and education. These findings suggest that mothers do tend to prolong breast feeding for undernourished children and reduce its duration for well-nourished infants. The lower nutritional status often reported among breast-fed infants is probably not due to any negative impact of prolonged breast feeding on growth, but rather to pre-existing differences.

Children's height, health and appetite influence mothers' weaning decisions in rural Senegal.

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.

Nutritional change and economic crisis in an urban Congolese community.

BACKGROUND: 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. METHODS: Two cross-sectional surveys were carried out on representative samples of Brazzaville children < 6 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 as < 18.5 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. RESULTS: 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. CONCLUSIONS: 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.

PIP: 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.

Decline of infant and child mortality rates in rural Senegal over a 37-year period (1963-1999).

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.

Seroconversions in unvaccinated infants: further evidence for subclinical measles from vaccine trials in Niakhar, Senegal.

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.

Child mortality following standard, medium or high titre measles immunization in West Africa.

BACKGROUND: The World Health Organization (WHO) recommended the use of high titre measles vaccine in 1989. Subsequent long term follow-up of several trials yielded results suggesting higher mortality among children inoculated with medium and high titre vaccines compared to standard titre vaccines, although none of the individual trials found significant differences in mortality. METHODS: Long term survival after standard, medium and high titre measles vaccines has been investigated in a combined analysis of all West African trials with mortality data. In trials from Guinea-Bissau, The Gambia and Senegal, children received medium or high titre vaccines from 4 months of age and were compared to control groups recruited at the same time later receiving standard titre vaccine from 9 months of age. All children were followed up to at least 3 years old. RESULTS: Combining trials of high titre vaccines showed higher mortality among the high titre group compared to the standard group: mortality ratio (MR) = 1.33 (95% CI : 1.02-1. 73). Mortality among recipients of medium titre vaccines was not different from that in the standard vaccine group, MR = 1.11 (95% CI: 0.54-2.27). In a combined analysis by sex, the adjusted mortality ratios comparing high titre vaccine with standard vaccine were 1.86 (95% CI : 1.28-2.70) for females and 0.91 (95% CI : 0.61-1.35) for males. The trials were not designed to study long term mortality. Adjustments for several possible sources of bias did not alter the results. CONCLUSIONS: The combined analysis showed a decreased survival related to high titre measles vaccine compared with standard titre vaccines, though solely among females. As a result of these studies from West Africa and a study from Haiti, WHO has recommended that high titre measles vaccine no longer be used.

PIP: A prospective survey of the use of high and medium-titre measles vaccine in Guinea-Bissau, the Gambia, and Senegal indicated that this regimen is associated with higher long-term child mortality than the standard titre vaccine. Children enrolled in trials in these three countries received medium or high-titre vaccines at three months of age and survival data were compared to findings from controls who received the standard titre at nine months of age. There were 339 deaths among the 3073 children (11,129 child-years) followed for up to three years of age. Combination of all West African data for medium and high-titre vaccines yielded a mortality rate of 1.21 (95% confidence interval, 0.89-1.63). The excess mortality was statistically significant at the p 0.05 level only when high-titre vaccine was compared to the standard regimen (1.33; 95% confidence interval, 1.02-1.73). No difference in mortality was found between medium or high-titre recipients and control children who had not yet received any vaccine. The excess mortality in the high-titre groups was restricted to females. There was no interaction between age and vaccine type. As a result of these findings, the World Health Organization reversed its 1989 recommendation for use of high-titre measles vaccine. Urged are community studies of measles-related morbidity and mortality that investigate the gender differential identified in this survey.

Protective efficacy of high-titre measles vaccines administered from the age of five months: a community study in rural Senegal.

Using data on incidence and secondary attack rates, we examined the protective efficacy of high-titre Edmonston-Zagreb (EZ) and Schwarz (SW-HT) measles vaccines administered at 5 months. Control children were assigned to placebo at age 5 months and standard Schwarz (SW-std) measles vaccine at 9-10 months of age. A large proportion of measles cases was verified serologically. Though high-titre vaccines seemed to be protective before 10 months of age, a significant reduction in disease could not be demonstrated due to low incidence of measles. After 10 months of age, SW-std given at 10 months gave a vaccine efficacy of 100% and induced better protection than SW-HT (P = 0.030) and EZ-HT (P = 0.128) administered at 5 months. In studies of secondary attack rates in the compound, vaccine efficacy was 91% (75%-97%) for EZ-HT, 85% (40%-96%) for SW-HT, and 100% for SW-std. Attack rates were correlated with intensity of exposure (P = 0.0006), being much higher for children exposed in the same hut than for those living in the same compound but in a different household (relative risk = 3.36 [1.32-8.57]). The attack rate was significantly lower among vaccinated than unvaccinated children with no detectable measles antibody (relative risk = 0.41 [0.18-0.93]). In rural areas with a high coverage in the surrounding community, a single dose at 9-10 months may provide sufficient protection. Since high-titre vaccines have been associated with higher mortality than SW-std, further improvements in measles control before 9 months may require two-dose strategies with standard vaccines.

A comparison of vaccine efficacy and mortality during routine use of high-titre Edmonston-Zagreb and Schwarz standard measles vaccines in rural Senegal.

Vaccine efficacy and mortality in successive cohorts of children who routinely received either Edmonston-Zagreb high-titre (EZ-HT) or Schwarz standard (SW-STD) measles vaccines have been examined in a rural area of Senegal. The 2 vaccines were equally protective against measles infection (vaccination efficacy: EZ-HT 94%; SW-STD 93%). Children who did not attend a scheduled session to receive measles vaccine had a higher mortality rate between 9 months and 2 years of age than did children receiving either EZ-HT (mortality ratio [MR] = 1.81, 95% confidence interval [CI] 1.06-3.08) or SW-STD measles vaccine (MR = 1.74, 95% CI 0.95-3.21). Children of either sex vaccinated with EZ-HT had lower mortality than their equivalents who had not received any measles vaccine. There was no difference in overall mortality between recipients of EZ-HT and SW-STD (MR = 0.96, 95% CI 0.70-1.30). Using a Cox regression analysis to adjust for sex, age and significant background factors (season and death of mother), mortality rates tended to be lower for male recipients of EZ-HT than for boys receiving SW-STD (MR = 0.73, 95% CI 0.50-1.11) and higher for girls receiving EZ-HT than for girls receiving SW-STD (MR = 1.30, 95% CI 0.81-2.09) (test of interaction between sex and vaccine, P = 0.067). The tendency to reduced survival benefit for girls following receipt of high-titre measles vaccines substantiated observations from randomized trials in Guinea-Bissau, Senegal and Haiti. Existing data provide little support for the notion that high-titre vaccine is deleterious but it may not have the same beneficial effects as standard-titre measles vaccine.

Infant feeding and nutritional status: the dilemma of mothers in rural Senegal.

OBJECTIVE: To describe infant feeding practices in rural Senegal in relation to age and nutritional status. The main hypothesis to be tested was whether mothers modulate feeding in response to growth and nutritional status of their infants. DESIGN: A cross-sectional survey using qualitative 24-h recalls and lifetime recalls to assess feeding practices, and using weight and recumbent length measurements to assess nutritional status. SETTING: Three health clinics in the Fatick region, a rural area of Senegal, West Africa, covering a population of 26,600. SUBJECTS: All 2-10-month-old infants attending four immunization sessions in 1991 (n = 1174; 80% of convoked infants). MAIN OUTCOME MEASURES: Prevalence of feeding with additional food (gruel, family diet and food of animal origin), weight-for-length and length-for-age. RESULTS: All infants were breastfed. A supplement had been given the day before the survey to 10% of infants aged 2-3.9 months, 30% of infants aged 4-5.9 months and 45% of those aged 6-6.9 months. The main food items were watery millet gruel and family diet (millet or rice). Gruel was given in response to perceived breast-milk insufficiency. Animal products were seldom eaten at any age. Length-for-age and weight-for-length were significantly lower among infants supplemented with millet gruel, when adjusted for age; while no such relationship was found with family diet. CONCLUSION: Mothers preferentially fed gruel to small, thin infants.

PIP: During immunization sessions in May, July, September, and December 1991 at three health clinics in the Fatick region in rural Senegal, interviews with mothers of 1174 infants 2-10 months old and anthropometric measurements of these infants were conducted to determine food consumption patterns according to age and to compare these patterns with the nutritional status of the infants. All the infants had been breast fed the day before the survey. No infant was exclusively breast fed, however. All infants were given water, most beginning with the first week of life. More than 25% of the infants had already consumed some additional food at least once at 3-3.9 months of age. 10% of infants 3-3.9 months old, 30% of those 4-5.9 months old, and 45% of those 6-6.9 months old had eaten other food the day before the survey. The most common food supplements were watery millet gruel and family diet (millet or rice). Mothers tended to give infants millet gruel because they perceived an insufficiency of breast milk. Their perception may have been correct because infants 2-3.9 months old who received millet gruel, but not the family diet, were both shorter and thinner than their counterparts (p 0.01). The nutritional status of infants 6-10.5 months old was essentially the same as the status of infants receiving additional food. Mothers gave additional food at irregular intervals. These findings suggest that low nutritional status may lead to supplementation with gruel. Future research should focus on weaning foods as well as on improvement in breast milk consumption in small, thin infants less than 6 months old.

Age at introduction of complementary food and physical growth from 2 to 9 months in rural Senegal.

OBJECTIVE: To compare nutritional status and physical growth among infants according to age at introduction of complementary food (CF). DESIGN: A longitudinal observational study. SETTING: Three health clinics in a rural area of Senegal. SUBJECTS: During immunization sessions, 522 infants were recruited at 2-3 months. Complete data on three visits were available for 420 infants (4 visits: n = 361); 73 were lost to follow-up and 29 had incomplete data. MAIN OUTCOME MEASURES: Increments in length and weight between adjacent visits. RESULTS: Infants complemented at 2-3 months (n = 50) had significantly lower length-for-age (P = 0.014), weight-for-length (P < 0.001) and arm circumference (P < 0.0001) at 2-3 months than predominantly breastfed infants (n = 370), after adjustment for residence, mother's age and education of parents. The growth in weight and length from 2-3 to 9-10 months did not differ. The infants complemented by 4-5 months, but not yet at 2-3 months, (n = 94) had a slightly lower length increment from 4-5 to 6-7 months (1.42 vs 1.53 cm/mo, p < 0.05) compared to infants predominantly breastfed at 4-5 months (n = 276). The infants first complemented by 6-7 months (n = 122) had increments from 6-7 to 9-10 months similar to those of predominantly breastfed infants (n = 154). CONCLUSION: Introduction of CF by 2-3 months was associated with a low nutritional status, but not with slow growth from 2-3 to 9-10 months. Introduction of CF by 4-5 months was associated with slightly slower linear growth compared to later introduction.

PIP: The impact of age at introduction of supplementary foods on nutritional status and physical growth was investigated in a longitudinal study of 420 infants recruited from 3 health clinics in rural Central Senegal. Infants were 2-3 months of age at admission and were followed up at 4-5, 6-7, and 9-10 months of age. The 50 infants who were receiving supplementary feeds at 2-3 months had significantly lower length-for-age, weight-for-length, and arm circumference at the initial visit than predominantly breast-fed infants after adjustments for residence, maternal age, and parental education. The 94 infants who began receiving complementary feeds at 4-5 months had a slightly lower length increment from 4-5 to 6-7 months compared with infants predominantly breast-fed at 4-5 months. Finally, the 122 infants first fed complementary foods at 6-7 months had increments from 6-7 to 9-10 months similar to those of the 154 infants who continued to be predominantly breast-fed. Infants complemented early, late, and very late had similar length-for-age and weight-for-length at 2-3 months, indicating that nutritional status prior to food introduction was not a determinant of age at introduction of complementary food. The growth data collected in this study confirm the importance of waiting until 6 months of age to introduce complementary foods.