Sero-epidemiological evaluation of changes in Plasmodium falciparum and Plasmodium vivax transmission patterns over the rainy season in Cambodia

Institute of Tropical Medicine, Nationalestraat 155, Antwerp 2000, Belgium.
Malaria Journal (Impact Factor: 3.11). 03/2012; 11(1):86. DOI: 10.1186/1475-2875-11-86
Source: PubMed


In Cambodia, malaria transmission is low and most cases occur in forested areas. Sero-epidemiological techniques can be used to identify both areas of ongoing transmission and high-risk groups to be targeted by control interventions. This study utilizes repeated cross-sectional data to assess the risk of being malaria sero-positive at two consecutive time points during the rainy season and investigates who is most likely to sero-convert over the transmission season.
In 2005, two cross-sectional surveys, one in the middle and the other at the end of the malaria transmission season, were carried out in two ecologically distinct regions in Cambodia. Parasitological and serological data were collected in four districts. Antibodies to Plasmodium falciparum Glutamate Rich Protein (GLURP) and Plasmodium vivax Merozoite Surface Protein-1(19) (MSP-1(19)) were detected using Enzyme Linked Immunosorbent Assay (ELISA). The force of infection was estimated using a simple catalytic model fitted using maximum likelihood methods. Risks for sero-converting during the rainy season were analysed using the Classification and Regression Tree (CART) method.
A total of 804 individuals participating in both surveys were analysed. The overall parasite prevalence was low (4.6% and 2.0% for P. falciparum and 7.9% and 6.0% for P. vivax in August and November respectively). P. falciparum force of infection was higher in the eastern region and increased between August and November, whilst P. vivax force of infection was higher in the western region and remained similar in both surveys. In the western region, malaria transmission changed very little across the season (for both species). CART analysis for P. falciparum in the east highlighted age, ethnicity, village of residence and forest work as important predictors for malaria exposure during the rainy season. Adults were more likely to increase their antibody responses to P. falciparum during the transmission season than children, whilst members of the Charay ethnic group demonstrated the largest increases.
In areas of low transmission intensity, such as in Cambodia, the analysis of longitudinal serological data enables a sensitive evaluation of transmission dynamics. Consecutive serological surveys allow an insight into spatio-temporal patterns of malaria transmission. The use of CART enabled multiple interactions to be accounted for simultaneously and permitted risk factors for exposure to be clearly identified.

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Available from: Umberto D'Alessandro
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    • "The most likely explanation seems that transmission is associated with some behavioural risk such as frequenting coastal areas for fishing where local vectors such as Anopheles sundaicus predominate in the south part of Lampung and/or for rubber tapping to forested areas where Anopheles kochi and Anopheles punctulatus are present in the northern part of Lampung. This behaviour change has been documented in other areas in Southeast Asia, such as Cambodia [18], where both social science and biological indicators implicate a significant increase in exposure with proximity to and/or travel to areas where local vectors persist. Temporal changes in socio-economic status of the population in Lampung may also be a determinant factor that contribute to the changes in malaria exposure as has been reported in the population in Central Vietnam [22], where the wealthier people are less exposed. "
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    ABSTRACT: 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. Filter-paper blood spot samples collected from Purworejo and Lampung by cross-sectional survey during high and low transmission season were stored at -20[degree sign]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. 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. 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.
    Full-text · Article · Dec 2013 · Malaria Journal
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    • "Due to the degree of sequence variability, it is recommended to use multiple antigens for each species in order to optimize the sensitivity of the antibody detection and to improve the identification of changes in malaria transmission over time in low transmission settings [20,38]. However, the observation that the antigens used in the study are relatively conserved [51] combined with results from recent studies performed in Cambodia, Vietnam and Peru suggests that PfGLURP and PvMSP119 are highly suitable for the detection of antibodies against P. falciparum and P. vivax, respectively [33,52]. Multiplexing the serological tests as well as standardizing the antigens used is of crucial importance for monitoring elimination efforts and comparing trends across countries and regions. "
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    ABSTRACT: Where malaria endemicity is low, control programmes need increasingly sensitive tools for monitoring malaria transmission intensity (MTI) and to better define health priorities. A cross-sectional survey was conducted in a low endemicity area of the Peruvian north-western coast to assess the MTI using both molecular and serological tools. Epidemiological, parasitological and serological data were collected from 2,667 individuals in three settlements of Bellavista district, in May 2010. Parasite infection was detected using microscopy and polymerase chain reaction (PCR). Antibodies to Plasmodium vivax merozoite surface protein-119 (PvMSP119) and to Plasmodium falciparum glutamate-rich protein (PfGLURP) were detected by ELISA. Risk factors for exposure to malaria (seropositivity) were assessed by multivariate survey logistic regression models. Age-specific antibody prevalence of both P. falciparum and P. vivax were analysed using a previously published catalytic conversion model based on maximum likelihood for generating seroconversion rates (SCR). The overall parasite prevalence by microscopy and PCR were extremely low: 0.3 and 0.9%, respectively for P. vivax, and 0 and 0.04%, respectively for P. falciparum, while seroprevalence was much higher, 13.6% for P. vivax and 9.8% for P. falciparum. Settlement, age and occupation as moto-taxi driver during previous year were significantly associated with P. falciparum exposure, while age and distance to the water drain were associated with P. vivax exposure. Likelihood ratio tests supported age seroprevalence curves with two SCR rather for both P. vivax and P. falciparum indicating significant changes in the MTI over time. The SCR for PfGLURP was 19-fold lower after 2002 as compared to before (lamda1 = 0.022 versus lamda2 = 0.431), and the SCR for PvMSP119 was four-fold higher after 2006 as compared to before (lamda1 = 0.024 versus lamda2 = 0.006) . Combining molecular and serological tools considerably enhanced the capacity of detecting current and past exposure to malaria infections and related risks factors in this very low endemicity area. This allowed for an improved characterization of the current human reservoir of infections, largely hidden and heterogeneous, as well as providing insights into recent changes in species specific MTIs. This approach will be of key importance for evaluating and monitoring future malaria elimination strategies.
    Full-text · Article · Sep 2013 · Malaria Journal
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    • "The results of the serological evaluations of antibody responses to P. falciparum and P. vivax in relation to risk factors is discussed in detail elsewhere [19]. The current study has focused on a possible relation between the entomological and parasitological or serological data only. "
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    ABSTRACT: Despite progress in malaria control, malaria remains an important public health concern in Cambodia, mostly linked to forested areas. Large-scale vector control interventions in Cambodia are based on the free distribution of long-lasting insecticidal nets (LLINs), targeting indoor- and late-biting malaria vectors only. The present study evaluated the vector density, early biting activity and malaria transmission of outdoor-biting malaria vectors in two forested regions in Cambodia. In 2005 two entomological surveys were conducted in 12 villages and their related forest plots in the east and west of Cambodia. Mosquitoes were collected outdoors by human landing collections and subjected to enzyme-linked immunosorbent assay (ELISA) to detect Plasmodium sporozoites after morphological identification. Blood samples were collected in the same villages for serological analyses. Collected data were analysed by the classification and regression tree (CART) method and linear regression analysis. A total of 11,826 anophelines were recorded landing in 787 man-night collections. The majority (82.9 %) were the known primary and secondary vectors. Most of the variability in vector densities and early biting rates was explained by geographical factors, mainly at village level. Vector densities were similar between forest and village sites. Based on ELISA results, 29 % out of 17 Plasmodium-positive bites occurred before sleeping time, and 65 % in the forest plots. The entomological inoculation rates of survey 1 were important predictors of the respective seroconversion rates in survey 2, whereas the mosquito densities were not. In Cambodia, outdoor malaria transmission in villages and forest plots is important. In this context, deforestation might result in lower densities of the primary vectors, but also in higher densities of secondary vectors invading deforested areas. Moreover, higher accessibility of the forest could result in a higher man-vector contact. Therefore, additional vector control measures should be developed to target outdoor- and early-biting vectors.
    Full-text · Article · Sep 2013 · Malaria Journal
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