Plasmodium falciparum prevalence has decreased substantially over the past 15 years. However, the impact of declining transmission on the development and maintenance of immunity to severe P. falciparum malaria is poorly understood. Pathogenesis of severe P. falciparum malaria has been attributed to PfEMP1, an antigen expressed on the surface of infected erythrocytes and a major target of protective immunity. Virulent PfEMP1 types include those with a Group A or Domain Cassette 8 (DC8) classification. Antibodies to these virulent PfEMP1 types contribute to immunity to severe malaria.
We aimed to quantify the antibody response to severe malaria PfEMP1 types and investigate the impact of declining malaria transmission on immunity to severe malaria.
In a cohort of 464 Papua New Guinean children recruited in 2013 (low transmission period), moderate seroprevalence of antibodies to domains of PfEMP1-DC8 and to P. falciparum isolates expressing virulent PfEMP1 types were observed. IgG levels to PfEMP1-DC8 domains were positively associated with recent P. falciparum infection and with age. IgG1 and IgG3 were the predominant IgG subclasses targeting PfEMP1-DC8 domains and IgG3 levels were positively associated with age. We compared antibody levels and sero-prevalence to those of a cohort of 206 children from the same area studied in 2004 during a higher transmission period. The decline in malaria transmission between 2004 and 2013 substantially compromised the acquisition of immunity to DC8-PfEMP1 domains and to P. falciparum isolates expressing virulent PfEMP1 types. Further studies will evaluate the impact on the functional activity of antibodies.
Our results could assist in the development of vaccines and surveillance tools for the identification of at-risk populations. We established that a significant proportion of PNG children could be at high risk of severe malaria if a rebound in malaria transmission occurred, emphasizing the need for active surveillance and additional tools for elimination