Abstract
BackgroundStudies of the association between the level of anti-malarial antibody and protection from malaria infection can yield conflicting results if they fail to take into account differences in the malaria transmission rate. This can occur because high malaria exposure may drive high antibody responses, leading to an apparent positive association between immune response and infection rate. The neonatal period provides a unique window to study the protective effects of antibodies, because waning maternally-derived antibodies lead to different levels of protection with time.MethodsThis study uses data from two well-defined infant cohorts in Western Kenya with different burdens of malaria transmission. Survival models were used to assess how the magnitude of maternally derived malaria-specific IgG antibody (to 24 malaria antigens measured using Luminex beads) affected the time-to-first Plasmodium falciparum infection (detected by PCR). In addition, mathematical models were used to assess how the frequency of malaria infection varied between the cohorts with different exposure levels.ResultsDespite differences in underlying malaria incidence in the two regions, there was no difference in time-to-first malaria infection between the cohorts. However, there was a significant period of protection observed in children with high initial MSP1 (42 kDa fragment)-specific antibody levels, but this protection was not observed in children with low antibody levels. Children from the high transmission cohort had both longer initial periods of protection from malaria (attributable to higher initial antibody levels), but more rapid time-to-first-infection once malaria specific maternal antibodies declined below protective levels (attributable to higher exposure rates).ConclusionThis study demonstrates the complex interaction between passive (maternally-derived) immunity and the degree of malaria exposure in infants. Children from regions of high malaria transmission had higher levels of maternally-derived antibodies in early life, which led to a significant protection for several months. However, once this immunity waned, the underlying higher frequency of infection was revealed. A better understanding of the interaction between malaria exposure, immunity, and transmission risk will assist in identifying protective immune responses in P. falciparum infection.
Highlights
Studies of the association between the level of anti-malarial antibody and protection from malaria infection can yield conflicting results if they fail to take into account differences in the malaria transmission rate
The trans-placental transfer of maternal IgG antibodies to infants plays a critical role in protection of infants from common childhood infections including malaria [11]. It is the presence but the levels of maternal antibodies in infants that correlate with protection from malaria [12, 13]. This suggests that neonatal antibody levels and malaria exposure present a unique opportunity to investigate the role of naturally acquired antibody in protection from P. falciparum infection
Given the higher malaria infection rate in malariahi, it is expected that time-to-first infection with
Summary
Studies of the association between the level of anti-malarial antibody and protection from malaria infection can yield conflicting results if they fail to take into account differences in the malaria transmission rate. If individuals vary significantly in their exposure to infection [6, 7], high levels of exposure may induce high levels of antibody responses, and sero-reactivity can sometimes be observed paradoxically as a risk factor for malaria [8, 9] This may explain why identification of protective immune responses may be more difficult than expected [10]. The trans-placental transfer of maternal IgG antibodies to infants plays a critical role in protection of infants from common childhood infections including malaria [11] It is the presence but the levels of maternal antibodies in infants that correlate with protection from malaria [12, 13] (reviewed in [14]). This may provide a ‘window’ in which the underlying level of exposure can be assessed in the absence of interference from different levels of maternal acquired immunity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
