Serological signatures of declining exposure following intensification of integrated malaria control in two rural Senegalese communities

Abstract

Recent control scale-up has reduced malaria in many areas but new tools are needed to monitor further progress, including indicators of decreasing exposure to parasite infection. Although serology is considered a promising approach in this regard, the serological impact of control interventions has been so far studied using indirect quantification of exposure. Cohort surveys concomitantly recording entomological and malariometric indices have been conducted in two Senegalese settings where supervised control intensification implemented in 2006 shifted malaria from historically holoendemic in Dielmo and mesoendemic in Ndiop to hypoendemic in both settings by 2013. We analyse here serological signatures of declining transmission using archived blood samples. Responses against ten pre-erythrocytic and erythrocytic antigens from Plasmodium falciparum and P. malariae alongside an Anopheles gambiae salivary gland antigen were analysed. Cross-sectional surveys conducted before (2002) and after (2013) control intensification showed a major impact of control intensification in both settings. The age-associated prevalence, magnitude and breadth of the IgG responses to all antigens were village-specific in 2002. In 2013, remarkably similar patterns were observed in both villages, with marginal responses against all parasite antigens in the 0-5y children and reduced responses in all previously seropositive age groups. Waning of humoral responses of individuals who were immune at the time of control intensification was studied from 2006 to 2013 using yearly samplings. Longitudinal data were analysed using the Cochran-Armittage trend test and an age-related reversible catalytic conversion model. This showed that the antigen-specific antibody declines were more rapid in older children than adults. There was a strong association of antibody decline with the declining entomological inoculation rate. We thus identified serological markers of declining exposure to malaria parasites that should help future monitoring of progress towards malaria elimination.

Evaluating antidisease immunity to malaria and implications for vaccine design

“…Similarly, higher seroprevalence and higher antibody titres were observed in children and adults immediately after the high‐transmission season (a period of intense exposure) relative to observed levels before the malaria season (a period of little to no transmission) 99. Two Senegalese studies also recently reported a decline in seroprevalence of antibodies to both pre‐erythrocytic and erythrocytic stage antigens in children, as the entomological inoculation rate (EIR) declined over the years 102, 103. Clearly, high exposure levels are associated with higher antibody levels, and children harbour higher parasitaemia before manifesting clinical symptoms 58, 61, 96.…”

“…99 Two Senegalese studies also recently reported a decline in seroprevalence of antibodies to both pre-erythrocytic and erythrocytic stage antigens in children, as the entomological inoculation rate (EIR) declined over the years. 102,103 Clearly, high exposure levels are associated with higher antibody levels, and children harbour higher parasitaemia before manifesting clinical symptoms. 58,61,96 This observation, however, raises a question: how is it that highly exposed children from endemic areas are able to prevent aggravated immunopathology which should, supposedly, ensue from comparatively higher antigenaemia (parasitaemia)?…”

Serological signatures of SARS-CoV-2 infection: Implications for antibody-based diagnostics

“…The challenge lies in selecting appropriate biomarkers and choosing between the increasing number of commercial assays, many of which have not been extensively validated and may produce conflicting results. The opportunity is that with multiple biomarkers, it is possible to generate a serological signature of infection that is robust to how antibody levels change over time [17][18][19][20], rather than relying on classification of sero-positive individuals using a single cutoff antibody level.…”

Practical example of multiple antibody screening for evaluation of malaria control strategies

“…before peak transmission in Dielmo (holoendemic area) and before the transmission season in Ndiop (meso-endemic). Overall 184 and 196 villagers in Dielmo, and 202 and 216 villagers in Ndiop were evaluated in 2002 and 2013, respectively with a sub-group of samples from 75 (Dielmo) and 86 (Ndiop) individuals who participated to both studies ( Table 2) [27]. After withdrawal, plasma and red blood cells were separated by centrifugation and stored at − 20 °C.…”

“…In this report, a practical example is provided as a snapshot cross-sectional picture using samples from symptomatic and asymptomatic cohorts in the Côte d'Ivoire and Senegal. A large panel of antigens were initially explored using the multiplex Luminex assay [25][26][27], here analysis was focused on 3 main antigen targets: (i) a preerythrocytic antigen LSA1 41 ; (ii) a merozoite antigen MSP1p19, and (iii) a whole schizont extract (SE: measured by standard ELISA) from a local strain adapted to in vitro culture [28], as a reference antigen for overall antibody response against P. falciparum. In the cohort from Senegal, antibody responses to six additional antigens are given with regards to the sero-catalytic models.…”