Safety and immunogenicity of RIX4414 live attenuated human rotavirus vaccine in adults, toddlers and previously uninfected infants.

A live attenuated human rotavirus (HRV) vaccine, strain RIX4414, was tested sequentially in adults, previously infected toddlers, and previously uninfected infants. A single dose was given to adults and toddlers and found well tolerated. Next, a dose ranging (three different viral concentrations) safety and immunogenicity study was conducted in rotavirus IgA antibody negative infants (N= 192), who received two doses of RIX4414 vaccine or placebo at 2 and 4 months of age. No side effects were seen after vaccination. Specifically, administration of RIX4414 vaccine was not temporally associated with fever, diarrhea, or increase in liver transaminases. Rotavirus IgA seroconversion ranged from 50 to 88% after one dose and from 73 to 96% after two doses, depending on vaccine titer. After the first dose, on days 7-9 post vaccination, between 38 and 60% of the infants shed the vaccine virus, whereas after the second dose only 0 to 13% of the vaccinees shed the vaccine virus. It is concluded that RIX4414 strain HRV vaccine is virtually non-reactogenic and, at high titer, highly immunogenic in susceptible infants.

Timing of growth faltering in rural Malawi.

AIM: To determine the timing of growth faltering among under 3 year old children. METHODS: Prospective population based cohort study in Lungwena, rural Malawi, southeast Africa. A total of 767 live born babies were regularly visited from birth until 3 years of age. Weight, height, and mid upper arm circumference were measured at monthly intervals until 18 months and at three month intervals thereafter. Growth charts were constructed using the LMS method and comparisons made to two international databases: the traditional United States National Center for Health Statistics/World Health Organisation (NCHS/WHO) reference and the recently developed 2000 Centers for Disease Control (CDC) growth reference. RESULTS: Compared to the 2000 CDC reference population, newborns in Lungwena were on average 2.5 cm shorter and 510 g lighter. On a population level, height faltering was present at birth and continued throughout the first three years. Weight faltering, on the other hand, occurred mainly between 3 and 12 months of age. At 36 months, the mean weight and height of the study children were 2.3 kg and 10.5 cm lower than those of the reference population, respectively. The results remained essentially similar when the comparisons were made to the NCHS/WHO reference. CONCLUSIONS: The fact that weight and height faltering do not follow identical time patterns suggests that they may have different origin and determinants. Further studies on the aetiology of height faltering and different approaches to preventive interventions are needed.

Seasonality of growth and the relationship between weight and height gain in children under three years of age in rural Malawi.

AIM: To describe the seasonal pattern of growth and analyse the relationship between weight and height gain in children under 3 y of age. METHODS: A population-based cohort of 767 children was prospectively followed from birth until 36 mo of age in rural Malawi, southeast Africa. Weight and height measurements were collected at monthly intervals until 18 mo of age and quarterly thereafter. Gains in weight and height and prevalence of malnutrition in different seasons were calculated. The relationship between weight and height gain was analysed using a series of correlation analyses. RESULTS: Both weight gain and linear growth velocity showed an age-dependent seasonal pattern. After infancy, periods of maximal or minimal height increments systematically occurred 3 mo after those for weight gain. The prevalence of malnutrition also followed a seasonal pattern, peaking a few months after periods of reduced growth. Despite the overall pattern, weight gain and subsequent linear growth were not correlated on an individual level. At any point, however, a child's weight for height was directly, albeit weakly, correlated to height gain in the subsequent 3-mo interval. CONCLUSION: Growth of children under 3 y of age followed an age-dependent seasonal pattern. The poor correlation between children's weight and height increments suggests that seasonality affected weight gain and linear growth through different mechanisms.

Male biased mortality among 1-2 year old children in rural Malawi.

We performed a community based cohort study in rural Malawi and documented a twofold mortality risk among 1-2 year old boys compared to girls of the same age. Because of its potential implications for child survival programmes, further studies should investigate whether sex differences in childhood mortality are more widespread in Sub-Saharan Africa.

Determinants of linear growth and predictors of severe stunting during infancy in rural Malawi.

UNLABELLED: Stunting is common among children under 5 y of age in sub-Saharan Africa. Several risk factors have been associated with poor growth but few studies have prospectively addressed the development of linear growth faltering and stunting during the first year of life. The present study was designed to analyse typical growth among rural Malawian infants, focusing particularly on the impact of birth size, adherence to feeding guidelines and morbidity in the development of severe stunting during infancy. A community-based cohort of 613 singleton newborns was prospectively followed by monthly home visits. Data were collected on the children's socioeconomic background, maternal size and weight gain during pregnancy, birth events, morbidity, breastfeeding and complementary feeding, growth and mortality. Univariate and multivariate analyses were used to determine associations between predictor variables and poor linear growth. The proportions of stunted infants (Height-for-age Z-score < -2) at 3, 6 and 9 mo of age were 27%, 51%, and 63%, respectively. At I y of age, over two-thirds (71%) of the infants were at least moderately (HAZ < -2) and 31% severely stunted (HAZ < -3). CONCLUSION: The strongest predictor of severe stunting at 12 mo of age was small birth size. Other variables independently associated with this outcome included inappropriate complementary feeding, high morbidity, maternal short stature, male gender, and home delivery. Faltering of linear growth started soon after birth and continued throughout infancy. Interventions increasing birth size could have a significant role in the prevention of early childhood stunting. The ideal strategy should also emphasize the importance of appropriate infant feeding and decreasing the number of illness episodes amongst the infants.