Serology reveals heterogeneity of Plasmodium falciparum transmission in northeastern South Africa: implications for malaria elimination

Abstract

Background: It is widely acknowledged that modifications to existing control interventions are required if South Africa is to achieve malaria elimination. Targeting indoor residual spraying (IRS) to areas where cases have been detected is one strategy currently under investigation in northeastern South Africa. This seroprevalence baseline study, nested within a targeted IRS trial, was undertaken to provide insights into malaria transmission dynamics in South Africa and evaluate whether sero-epidemiological practices have the potential to be routinely incorporated into elimination programmes.

Methods: Filter-paper blood spots, demographic and household survey data were collected from 2710 randomly selected households in 56 study wards located in the municipalities of Ba-Phalaborwa and Bushbuckridge. Blood spots were assayed for Plasmodium falciparum apical membrane antigen-1 and merozoite surface protein-1₁₉ blood-stage antigens using an enzyme linked immunosorbent assay. Seroprevalence data were analysed using a reverse catalytic model to determine malaria seroconversion rates (SCR). Geospatial cluster analysis was used to investigate transmission heterogeneity while random effects logistic regression identified risk factors associated with malaria exposure.

Results: The overall SCR across the entire study site was 0.012 (95% CI 0.008-0.017) per year. Contrasting SCRs, corresponding to distinct geographical regions across the study site, ranging from <0.001 (95% CI <0.001-0.005) to 0.022 (95% CI 0.008-0.062) per annum revealed prominent transmission heterogeneity. Geospatial cluster analysis of household seroprevalence and age-adjusted antibody responses detected statistically significant (p < 0.05) spatial clusters of P. falciparum exposure. Formal secondary education was associated with lower malaria exposure in the sampled population (AOR 0.72, 95% CI 0.56-0.95, p = 0.018).

Conclusions: Although overall transmission intensity and exposure to malaria was low across both study sites, malaria transmission intensity was highly heterogeneous and associated with low socio-economic status in the region. Findings suggest focal targeting of interventions has the potential to be an appropriate strategy to deploy in South Africa. Furthermore, routinely incorporating sero-epidemiological practices into elimination programmes may prove useful in monitoring malaria transmission intensity in South Africa, and other countries striving for malaria elimination.

Keywords: Elimination; Heterogeneity; Hotspot; Malaria; PfAMA-1; PfMSP-119; Serology; South Africa; Transmission.

Fig. 1

Location of the study sites situated within the municipalities of Ba-Phalaborwa and Bushbuckridge in northeastern South Africa. Passively reported malaria incidence data was obtained from health facilities between 2010 and 2015 then averaged among study site wards [43]

Fig. 2

Plasmodium falciparum age-seroprevalence curves for the entire study site (a) and distinct geographical regions within each study site (b, c). Seroprevalence curves, fitted by maximum likelihood, represent the average annual rate at which this population become seropositive to either PfAMA-1 and/or PfMSP-1₁₉ characterized by a seroconversion rate (SCR). Red triangles: observed age-seroprevalence, solid lines: predicted seroprevalence and dotted lines: predicted seroprevalence upper and lower 95% confidence intervals. N: sample size

Fig. 3

Spatial analyses of household P. falciparum seroprevalance across the Ba-Phalaborwa and Bushbuckridge study sites. a Spatial distribution of households containing ≥1 PfAMA-1 and/or PfMSP-1₁₉ seropositive individual(s). SaTScan™ derived statistically significant (p-values <0.05) clusters of seropositive households reveal regions where there are a higher number of seropositive households than expected. b Spatial distribution of households containing ≥1 PfAMA-1 and/or PfMSP-1₁₉ seropositive individual(s) aged 5 years and under

Fig. 4

Spatial analyses of household-averaged, age-adjusted antibody responses to PfAMA-1 (a) and PfMSP-1₁₉ (b) across the Ba-Phalaborwa and Bushbuckridge study sites. Age-adjusted antibody responses were derived from log-transformed PfAMA-1/PfMSP-1₁₉ normalized OD values adjusted at 30 years. The resultant residual values were categorized as: as ‘lower than average’ (−2.370 to −0.499), ‘average’ (−0.500 to 0.500), ‘slightly higher than average’ (0.501–1.250), ‘higher than average’ (1.251–2.000) and ‘much higher than average’ (2.001–2.936). Statistically significant clusters (p-values < 0.05) of higher than average age-adjusted PfAMA-1/PfMSP-1₁₉ antibody responses are also shown

Fig. 5

Scatter plot of average reported malaria incidence per study ward between 2010 and 2015 and average study ward elevation. Elevation in metres from sea level. Slope: −0.006, r: −0.58

Fig. 6

Scatter plot of average reported malaria incidence per study ward between 2010 and 2015 and study ward seroprevalence. Ward-level seroprevalence corresponds to the percentage of sampled seropositive households in each ward