Application of Serological Tools and Spatial Analysis to Investigate Malaria Transmission Dynamics in Highland Areas of Southwest Uganda

BackgroundMalaria transmission is highly heterogeneous, especially in low endemic countries, such as Cambodia. This results in geographical clusters of residual transmission in the dry, low transmission season, which can fuel the transmission to wider areas or populations during the wet season. A better understanding of spatial clustering of malaria can lead to a more efficient, targeted strategy to reduce malaria transmission. This study aims to evaluate the potential of the use of serological markers to define spatial patterns in malaria exposure.MethodsBlood samples collected in a community-based randomized trial performed in 98 high endemic communities in Ratanakiri province, north-eastern Cambodia, were screened with a multiplex serological assay for five serological markers (three Plasmodium falciparum and two Plasmodium vivax). The antibody half-lives range from approximately six months until more than two years. Geographical heterogeneity in malaria transmission was examined using a spatial scan statistic on serology, PCR prevalence and malaria incidence rate data. Furthermore, to identify behavioural patterns or intrinsic factors associated with malaria exposure (antibody levels), risk factor analyses were performed by using multivariable random effect logistic regression models. The serological outcomes were then compared to PCR prevalence and malaria incidence data.ResultsA total of 6502 samples from two surveys were screened in an area where the average parasite prevalence estimated by PCR among the selected villages is 3.4 %. High-risk malaria pockets were observed adjacent to the ‘Tonle San River’ and neighbouring Vietnam for all three sets of data (serology, PCR prevalence and malaria incidence rates). The main risk factors for all P. falciparum antigens and P. vivax MSP1.19 are age, ethnicity and staying overnight at the plot hut.ConclusionIt is possible to identify similar malaria pockets of higher malaria transmission together with the potential risk factors by using serology instead of PCR prevalence or malaria incidence data. In north-eastern Cambodia, the serological markers show that malaria transmission occurs mainly in adults staying overnight in plot huts in the field. Pf.GLURP.R2 showed a shrinking pocket of malaria transmission over time, and Pf.MSP1.19, CSP, PvAMA1 were also informative for current infection to a lesser extent. Therefore, serology could contribute in future research. However, further in-depth research in selecting the best combination of antigens is required.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1558-1) contains supplementary material, which is available to authorized users.

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Geographical patterns of malaria transmission based on serological markers for falciparum and vivax malaria in Ratanakiri, Cambodia

Kerkhof

Sluydts

Heng

et al. 2016

“…As expected, on a population level, the occurrence of seroconversion and seroreversion events tracked with changes in the number of observed infection events, with higher incidence of malaria associated with a higher number of seroconversions for both antibodies [ 4 , 10 , 12 , 20 , 33 ]. The increase in seroconversion events and decrease in seroreversion events between 2011 and 2012 and 2012 and 2013 corresponded with a twofold increase in the number of observed malaria infections.…”

Section: Discussionsupporting

confidence: 64%

“…Since antibodies persist longer in the human body than the parasite itself (longer, too, than the lifespan of the vector), serological markers may represent more robust and sensitive measurements of transmission intensity than entomological or parasitological markers [ 4 – 6 ]. The utility of sero-epidemiological surveillance has been demonstrated by numerous studies in Tanzania [ 7 , 8 ], Vanuatu [ 9 ], Equatorial Guinea [ 10 ], Brazil [ 11 ], and Uganda [ 12 ]. The most widely studied markers include antigens to the Plasmodium falciparum apical membrane antigen 1 (AMA-1) and merozoite surface protein 1 (MSP-1 19 ) recombinant proteins, both of which have been proposed as malaria vaccine candidates [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

A longitudinal cohort study of malaria exposure and changing serostatus in a malaria endemic area of rural Tanzania

Simmons

Mboera

Miranda

et al. 2017

Self Cite

BackgroundMeasurements of anti-malarial antibodies are increasingly used as a proxy of transmission intensity. Most serological surveys are based on the use of cross-sectional data that, when age-stratified, approximates historical patterns of transmission within a population. Comparatively few studies leverage longitudinal data to explicitly relate individual infection events with subsequent antibody responses.MethodsThe occurrence of seroconversion and seroreversion events for two Plasmodium falciparum asexual stage antigens (MSP-1 and AMA-1) was examined using three annual measurements of 691 individuals from a cohort of individuals in a malaria-endemic area of rural east-central Tanzania. Mixed-effect logistic regression models were employed to determine factors associated with changes in serostatus over time.ResultsWhile the expected population-level relationship between seroprevalence and disease incidence was observed, on an individual level the relationship between individual infections and the antibody response was complex. MSP-1 antibody responses were more dynamic in response to the occurrence and resolution of infection events than AMA-1, while the latter was more correlated with consecutive infections. The MSP-1 antibody response to an observed infection seemed to decay faster over time than the corresponding AMA-1 response. Surprisingly, there was no evidence of an age effect on the occurrence of a conversion or reversion event.ConclusionsWhile the population-level results concur with previously published sero-epidemiological surveys, the individual-level results highlight the more complex relationship between detected infections and antibody dynamics than can be analysed using cross-sectional data. The longitudinal analysis of serological data may provide a powerful tool for teasing apart the complex relationship between infection events and the corresponding immune response, thereby improving the ability to rapidly assess the success or failure of malaria control programmes.

“…The present results demonstrate that seroprevalence can be used as an additional tool to identify new areas of vivax malaria transmission. This information as well as the prevalence of all malaria species will likely prove essential for the successful implementation of malaria control and elimination programmes [27, 33]. …”

Section: Resultsmentioning

confidence: 99%

The hide and seek of Plasmodium vivax in West Africa: report from a large-scale study in Beninese asymptomatic subjects

Poirier

Doderer-Lang

Atchade

et al. 2016

Background Plasmodium vivax is considered to be absent from western Africa, where the prevalence of Duffy-negative red blood cell phenotype proves to be high. Several studies have, however, detected P. vivax infection cases in this part of Africa, raising the question of what is the actual prevalence of P. vivax in local populations. MethodsThe presence of P. vivax was investigated in a large population of healthy blood donors in Benin using microscopy, serology and molecular detection. The seroprevalence was measured with species-specific ELISA using two recombinant P. vivax proteins, namely rPvMSP1 and rPvCSP1. Specific molecular diagnosis of P. vivax infection was carried out using nested-PCR. The performances and cut-off values of both rPvCSP1 and rPvMSP1 ELISA were first assessed using sera from P. vivax-infected patients and from non-exposed subjects.ResultsAmong 1234 Beninese blood donors, no parasites were detected when using microscopy, whereas 28.7% (354/1234) of patients exhibited had antibodies against rPvMSP1, 21.6% (266/1234) against rPvCSP1, and 15.2% (187/1234) against both. Eighty-four samples were selected for nested-PCR analyses, of which 13 were positive for P. vivax nested-PCR and all Duffy negative. ConclusionThe results of the present study highlight an unexpectedly high exposure of Beninese subjects to P. vivax, resulting in sub-microscopic infections. This suggests a probably underestimated and insidious parasite presence in western Africa. While the vaccination campaigns and therapeutic efforts are all focused on Plasmodium falciparum, it is also essential to consider the epidemiological impact of P. vivax.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1620-z) contains supplementary material, which is available to authorized users.