Serological markers suggest heterogeneity of effectiveness of malaria control interventions on Bioko Island, equatorial Guinea

Abstract

Background: In order to control and eliminate malaria, areas of on-going transmission need to be identified and targeted for malaria control interventions. Immediately following intense interventions, malaria transmission can become more heterogeneous if interventions are more successful in some areas than others. Bioko Island, Equatorial Guinea, has been subject to comprehensive malaria control interventions since 2004. This has resulted in substantial reductions in the parasite burden, although this drop has not been uniform across the island.

Methods/principal findings: In 2008, filter paper blood samples were collected from 7387 people in a cross-sectional study incorporating 18 sentinel sites across Bioko, Equatorial Guinea. Antibodies were measured to P. falciparum Apical Membrane Antigen-1 (AMA-1) by Enzyme Linked Immunosorbent Assay (ELISA). Age-specific seropositivity rates were used to estimate seroconversion rates (SCR). Analysis indicated there had been at least a 60% decline in SCR in four out of five regions on the island. Changes in SCR showed a high degree of congruence with changes in parasite rate (PR) and with regional reductions in all cause child mortality. The mean age adjusted concentration of anti-AMA-1 antibodies was mapped to identify areas where individual antibody responses were higher than expected. This approach confirmed the North West of the island as a major focus of continuing infection and an area where control interventions need to be concentrated or re-evaluated.

Conclusion/interpretation: Both SCR and PR revealed heterogeneity in malaria transmission and demonstrated the variable effectiveness of malaria control measures. This work confirms the utility of serological analysis as an adjunct measure for monitoring transmission. Age-specific seroprevalence based evidence of changes in transmission over time will be of particular value when no baseline data are available. Importantly, SCR data provide additional evidence to link malaria control activities to contemporaneous reductions in all-cause child mortality.

Figure 1. Location of the 18 sentinel sites used for monitoring and evaluation of the BIMCP.

Source: Kleinschmidt et al (2007) . Regions are highlighted in boxes. 1- Malabo 2- North West 3- North East 4- South East and 5-South West.

Figure 2. Profile likelihood plots and age-seroprevalence for anti- P.falciparum AMA-1 antibody responses by region.

Panels 1–5a show univariate profile likelihood to evaluate the time at which seroconversion rates changed for each region 1 to 5 (1-Malabo, 2-North West, 3-North East, 4-South East 5-South West). The broken black line is the 95th percentile of the Chi-squared on 1 degree of freedom below the maximum. The two points at which this line crosses the log-likelihood profile either side of the age at which the likelihood is closest to 0 are used to determine an approximate 95% confidence interval for the time since the change. Panels 1–5b show age seroprevalence plots for anti- P.falciparum AMA-1 antibody responses fitted by maximum likelihood with a two forces of infection for each region 1–5. Red triangles represent observed data and blue lines predicted values. Dotted blue lines represent upper and lower 95% CI for the predicted SCR. The steepness of the slope of the line represents the rate of transmission which for regions 1(Malabo), 3(North East), 4(South East) and 5(South West) show a significant reduction in recent years.

Figure 3. Median anti- P.falciparum AMA-1 antibody titres by age group by region.

Figure 4. Spatial analyses of parasite positive individuals and anti- P.falciparum AMA-1 antibody responses.

4a Spatial distribution of parasite positive individuals under the age of 5 years. This age group was chosen to highlight children who had become infected since interventions began. Colour scale used to denote how many infections were present per household. Black dots are households with no infections in children under 5 years old. SaTScan was used to detect clusters (of no more than 5 km diameter) where there were higher numbers of cases than expected. The primary cluster (most significant cluster) is circled in red, with a secondary clusters circled in black (all p values less than 0.01 for clusters). 4b Spatial distribution of the residual mean log antibody responses to P.falciparum AMA-1 in all ages plotted by household. Red circle (AbC1) indicates a cluster of significantly higher than expected antibody responses detected using SaTScan. Secondary clusters (AbC 2–6) are circled in black. 4c Spatial distribution of the residual mean log antibody responses to P.falciparum AMA-1 in children under 5 plotted by household. Red circle (Ab<5C1) indicates a cluster of significantly higher than expected antibody responses detected using SaTScan.