Seasonal changes in the antibody responses against Plasmodium falciparum merozoite surface antigens in areas of differing malaria endemicity in Indonesia.

BACKGROUND: The transmission of malaria in Indonesia is highly heterogeneous spatially and seasonally. Anti-malaria antibody responses can help characterize this variation. In the present study antibody responses to Plasmodium falciparum MSP-1 and AMA-1 were measured to assess the transmission intensity in a hypo-endemic area of Purworejo and a meso-endemic area of Lampung during low and high transmission seasons. METHODS: Filter-paper blood spot samples collected from Purworejo and Lampung by cross-sectional survey during high and low transmission season were stored at -20°C. Indirect ELISA assays were carried out using PfMSP1-19 and PfAMA1 antigens. A positivity threshold was determined by samples from local unexposed individuals, and the differences in seroprevalence, antibody level and correlation between antibody level and age in each site were statistically analysed. RESULTS: Prevalence of antibodies to either PfMSP1-19 or PfAMA1 was higher in Lampung than in Purworejo in both the low (51.3 vs 25.0%) and high transmission season (53.9 vs 37.5%). The magnitude of antibody responses was associated with increasing age in both sites and was higher in Lampung. Age-adjusted seroconversion rates showed an approximately ten-fold difference between Lampung and Purowejo. Two different seroconversion rates were estimated for Lampung suggesting behaviour-related differences in exposure. In both settings antibody responses to PfMSP1-19 were significantly lower in the low season compared to the high season. CONCLUSION: Seasonal changes may be detectable by changes in antibody responses. This is particularly apparent in lower transmission settings and with less immunogenic antigens (in this case PfMSP1-19). Examination of antibody levels rather than seroprevalence is likely to be a more sensitive indicator of changes in transmission. These data suggest that sero-epidemiological analysis may have a role in assessing short-term changes in exposure especially in low or seasonal transmission settings

YG200608091218_3

BACKGROUND: Outside of Africa, P. falciparum and P. vivax usually coexist. In such co-endemic regions, successful malaria control programs have a greater impact on reducing falciparum malaria, resulting in P. vivax becoming the predominant species of infection. Adding to the challenges of elimination, the dormant liver stage complicates efforts to monitor the impact of ongoing interventions against P. vivax. We investigated molecular approaches to inform the respective transmission dynamics of P. falciparum and P. vivax and how these could help to prioritize public health interventions. METHODOLOGY/PRINCIPAL FINDINGS: Genotype data generated at 8 and 9 microsatellite loci were analysed in 168 P. falciparum and 166 P. vivax isolates, respectively, from four co-endemic sites in Indonesia (Bangka, Kalimantan, Sumba and West Timor). Measures of diversity, linkage disequilibrium (LD) and population structure were used to gauge the transmission dynamics of each species in each setting. Marked differences were observed in the diversity and population structure of P. vivax versus P. falciparum. In Bangka, Kalimantan and Timor, P. falciparum diversity was low, and LD patterns were consistent with unstable, epidemic transmission, amenable to targeted intervention. In contrast, P. vivax diversity was higher and transmission appeared more stable. Population differentiation was lower in P. vivax versus P. falciparum, suggesting that the hypnozoite reservoir might play an important role in sustaining local transmission and facilitating the spread of P. vivax infections in different endemic settings. P. vivax polyclonality varied with local endemicity, demonstrating potential utility in informing on transmission intensity in this species. CONCLUSIONS/SIGNIFICANCE: Molecular approaches can provide important information on malaria transmission that is not readily available from traditional epidemiological measures. Elucidation of the transmission dynamics circulating in a given setting will have a major role in prioritising malaria control strategies, particularly against the relatively neglected non-falciparum species

Details of parasite sampling.

<p>^1–9 Superscript indicates the number of patients with missing data.</p><p>Details of parasite sampling.</p

Linkage disequilibrium.

<p>Only samples with no missing data are included in the analyses. All nine loci were used in all <i>P</i>. <i>vivax</i> populations. In the <i>P</i>. <i>falciparum</i> populations, 8 loci were analysed in Bangka and Sumba, 6 in Kalimantan (exclusion of monomorphic loci TA42 and TA60), and 7 loci in West Timor (exclusion of monomorphic loci TA1).</p><p>¹ Restricted multi-locus haplotypes from samples with no more than one multi-allelic locus.</p><p>^NS Not significant (<i>P</i> > 0.05)</p><p>* <i>P</i> < 0.05</p><p>** <i>P</i> < 0.01</p><p>*** <i>P</i> < 0.001.</p><p>Linkage disequilibrium.</p

Unrooted neighbour-joining tree illustrating the genetic relatedness between <i>P</i>. <i>falciparum</i> (top) and <i>P</i>. <i>vivax</i> (bottom) isolates.

<p>Unrooted neighbour-joining tree illustrating the genetic relatedness between <i>P</i>. <i>falciparum</i> (top) and <i>P</i>. <i>vivax</i> (bottom) isolates.</p

Population structure in <i>P</i>. <i>vivax</i>.

<p>Bar plots illustrating the population structure at <i>K</i> = 2–5 in <i>P</i>. <i>vivax</i>. <i>K</i>1 = light green, <i>K</i>2 = dark green, <i>K</i>3 = red, <i>K</i>4 = orange, and <i>K</i>5 = white.</p

Within-host and population diversity.

<p>Within-host and population diversity.</p