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Acquisition of natural humoral immunity to P. falciparum in early life in Benin: impact of clinical, environmental and host factors

View Article: PubMed Central - PubMed

ABSTRACT

To our knowledge, effects of age, placental malaria infection, infections during follow-up, nutritional habits, sickle-cell trait and individual exposure to Anopheles bites were never explored together in a study focusing on the acquisition of malaria antibody responses among infants living in endemic areas.Five hundred and sixty-seven Beninese infants were weekly followed-up from birth to 18 months of age. Immunoglobulin G (IgG), IgG1 and IgG3 specific for 5 malaria antigens were measured every 3 months. A linear mixed model was used to analyze the effect of each variable on the acquisition of antimalarial antibodies in 6-to18-month old infants in univariate and multivariate analyses. Placental malaria, nutrition intakes and sickle-cell trait did not influence the infant antibody levels to P. falciparum antigens. In contrary, age, malaria antibody levels at birth, previous and present malaria infections as well as exposure to Anopheles bites were significantly associated with the natural acquisition of malaria antibodies in 6-to18-month old Beninese infants. This study highlighted inescapable factors to consider simultaneously in an immuno-epidemiological study or a vaccine trial in early life.

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Related in: MedlinePlus

Level of IgG1 specific to MSP3 predicted by the mixed linear model IgG1 specific to MSP3 levels are the residuals of adjustments (cf Materials and Methods -Outcome variable).The effect of an infection at each 3-month period is estimated in presence or not of an interaction between age and infection. The best fitted model includes an interaction between age and infection: the difference between the 2 curves increases with age illustrating that more an infant is old and stronger is his response to a first malaria infection.
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f4: Level of IgG1 specific to MSP3 predicted by the mixed linear model IgG1 specific to MSP3 levels are the residuals of adjustments (cf Materials and Methods -Outcome variable).The effect of an infection at each 3-month period is estimated in presence or not of an interaction between age and infection. The best fitted model includes an interaction between age and infection: the difference between the 2 curves increases with age illustrating that more an infant is old and stronger is his response to a first malaria infection.

Mentions: Table 1 shows the final model for each antibody response in infants aged more than six months. Overall, age, malaria specific antibody levels in cord blood and at 3 months, an infection having occurred either at the 3-month period or at the 3-to-6-month period before antibody measurement and environmental factors were significantly associated with the acquisition of antigen-specific IgG (data not shown), IgG1 and IgG3 in 6-to-18-month old infants. Age has a polynomial effect and, after a decrease from 6 to 9 or 12 months (depending on antibody), all the levels increased regularly until the age of 18 months (data not shown) as illustrated by the raw data in Fig. 1. Infections at 3–6 months of age were not significant, probably due to the immaturity of the newborn immune system and to the amount of maternal antibodies that could hide the slow acquisition. Contrarily, infections occurring either at the 3-month period or at the 3-to-6-month period before antibody measurement were positively significantly associated with the levels of antibodies. However, the effects of age and of infection on the evolution of antibody levels are complex, and a strong interaction (p < 10−3 for each antibody response) was detected between age and infections. This result is consistent with the fact that an infection occurring later in the follow-up had a stronger effect on the antibody response than an infection occurring early after birth when the immune system can be considered as less mature (Fig. 4). This effect of age has been already shown by Baird et al., who hypothesized that heavy exposure to infection among children, whether recent or lifelong, does not induce adult-like protection due to the maturation of adult immune system compared with infants3. However, we also showed that infection having occurred at the 3-to-6-month period before antibody measurement significantly increased the antibody response showing that the repetitions of infections and, indirectly the delay from the last infection, is an important factor in the acquisition of immunity. The environmental variable was very often significantly associated with high antibody levels (Table 1). Placental malaria and sickle-cell trait were not significant in the multivariate analyses.


Acquisition of natural humoral immunity to P. falciparum in early life in Benin: impact of clinical, environmental and host factors
Level of IgG1 specific to MSP3 predicted by the mixed linear model IgG1 specific to MSP3 levels are the residuals of adjustments (cf Materials and Methods -Outcome variable).The effect of an infection at each 3-month period is estimated in presence or not of an interaction between age and infection. The best fitted model includes an interaction between age and infection: the difference between the 2 curves increases with age illustrating that more an infant is old and stronger is his response to a first malaria infection.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037375&req=5

f4: Level of IgG1 specific to MSP3 predicted by the mixed linear model IgG1 specific to MSP3 levels are the residuals of adjustments (cf Materials and Methods -Outcome variable).The effect of an infection at each 3-month period is estimated in presence or not of an interaction between age and infection. The best fitted model includes an interaction between age and infection: the difference between the 2 curves increases with age illustrating that more an infant is old and stronger is his response to a first malaria infection.
Mentions: Table 1 shows the final model for each antibody response in infants aged more than six months. Overall, age, malaria specific antibody levels in cord blood and at 3 months, an infection having occurred either at the 3-month period or at the 3-to-6-month period before antibody measurement and environmental factors were significantly associated with the acquisition of antigen-specific IgG (data not shown), IgG1 and IgG3 in 6-to-18-month old infants. Age has a polynomial effect and, after a decrease from 6 to 9 or 12 months (depending on antibody), all the levels increased regularly until the age of 18 months (data not shown) as illustrated by the raw data in Fig. 1. Infections at 3–6 months of age were not significant, probably due to the immaturity of the newborn immune system and to the amount of maternal antibodies that could hide the slow acquisition. Contrarily, infections occurring either at the 3-month period or at the 3-to-6-month period before antibody measurement were positively significantly associated with the levels of antibodies. However, the effects of age and of infection on the evolution of antibody levels are complex, and a strong interaction (p < 10−3 for each antibody response) was detected between age and infections. This result is consistent with the fact that an infection occurring later in the follow-up had a stronger effect on the antibody response than an infection occurring early after birth when the immune system can be considered as less mature (Fig. 4). This effect of age has been already shown by Baird et al., who hypothesized that heavy exposure to infection among children, whether recent or lifelong, does not induce adult-like protection due to the maturation of adult immune system compared with infants3. However, we also showed that infection having occurred at the 3-to-6-month period before antibody measurement significantly increased the antibody response showing that the repetitions of infections and, indirectly the delay from the last infection, is an important factor in the acquisition of immunity. The environmental variable was very often significantly associated with high antibody levels (Table 1). Placental malaria and sickle-cell trait were not significant in the multivariate analyses.

View Article: PubMed Central - PubMed

ABSTRACT

To our knowledge, effects of age, placental malaria infection, infections during follow-up, nutritional habits, sickle-cell trait and individual exposure to Anopheles bites were never explored together in a study focusing on the acquisition of malaria antibody responses among infants living in endemic areas.Five hundred and sixty-seven Beninese infants were weekly followed-up from birth to 18 months of age. Immunoglobulin G (IgG), IgG1 and IgG3 specific for 5 malaria antigens were measured every 3 months. A linear mixed model was used to analyze the effect of each variable on the acquisition of antimalarial antibodies in 6-to18-month old infants in univariate and multivariate analyses. Placental malaria, nutrition intakes and sickle-cell trait did not influence the infant antibody levels to P. falciparum antigens. In contrary, age, malaria antibody levels at birth, previous and present malaria infections as well as exposure to Anopheles bites were significantly associated with the natural acquisition of malaria antibodies in 6-to18-month old Beninese infants. This study highlighted inescapable factors to consider simultaneously in an immuno-epidemiological study or a vaccine trial in early life.

No MeSH data available.


Related in: MedlinePlus