Effectiveness of a serological tool to predict malaria transmission intensity in an elimination setting

Abstract

Background: Sri Lanka achieved the WHO certificate as a malaria free country in September 2016, thus monitoring of malaria transmission using sensitive and effective tools is an important need. Use of age-specific antibody prevalence as a serological tool to predict transmission intensity is proven to be a cost effective and reliable method under elimination settings. This paper discusses the correlation of four anti-malarial antibodies against vivax and falciparum malaria with the declining transmission intensities in two previously high malaria endemic districts i.e. Kurunegala and Moneragala of Sri Lanka.

Methods: Sera was collected from 1,186 individuals from the two districts and were subjected to standard ELISA together with control sera from non-immune individuals to obtain Optical Density (OD) values for four anti-malarial antibodies i.e. anti-MSP1 and anti-AMA1 for both Plasmodium vivax and Plasmodium falciparum. The sero-positive samples were determined as mean OD + 3SD of the negative controls. The sero-prevalence was analyzed against the demographic characteristics of the population. A simple reversible catalytic model was fitted into sero-prevalence data to predict the sero-conversion and sero-reversion rates.

Results: Over 60% of the population was sero-positive for one or more antibodies except young children (<10 years). The sero-prevalence was zero in young children and very low in young adults when compared to the older age groups. The model developed for falciparum malaria that assumed the presence of a change in transmission was not significant in the Kurunegala district although significant reduction in transmission was observed when the model was used for P. vivax antibody data in that district. In Moneragala district however, all the serological markers indicated a change in transmission that has occurred approximately 15 years ago.

Conclusions: Assessment of MSP1 and AMA1 anti-malarial antibodies of P. vivax and P. falciparum proved to be useful indicators in predicting transmission under elimination settings as prevailed in Sri Lanka. The sero-conversion rates for the two districts studied are shown to be very low or zero indicating the absence of active and/or hidden transmission confirming a "true" state of elimination at least, in the two study districts in Sri Lanka.

Keywords: Anti-malarial antibodies; ELISA; Reversible catalytic model; Sero-positivity; Sri Lanka.

Fig. 1

Number of malaria cases reported 1985–2008. National data on P. vivax, P. falciparum and total number of malaria cases reported from 1985 to 2008 is given

Fig. 2

Maps of the study sites. Kurunegala district and Moneragala district. The selected DS divisions of the two districts are numbered and highlighted. Twelve DS divisions were selected from Kurunegala district (i.e. 1. Galgamuwa, 2. Polpithigama, 3. Ganewatta, 4. Ibbagamuwa, 5. Rideegama, 6. Panduwasnuwara, 7. Udabaddawa, 8. Kuliyapitiya West, 9. Kuliyapitiya East, 10. Narammala, 11. Weerambugedara and 12. Bamunukotuwa). From Moneragala district 4 DS divisions were selected (i.e. 1. Moneragala, 2. Buttala, 3. Kataragama, 4. Thanamalwila)

Fig. 3

Age specific sero-prevalence curves for each tested antibody. Age specific sero-prevalence curves for Kurunegala (a-b) and Moneragala (c-d) districts for P. vivax and P. falciparum antibodies. Each graph shows the age specific sero-prevalence where the dots represent the observed sero-prevalence when the age distributions were divided into the respective 10%-centiles. Reversible catalytic models assuming a constant transmission intensity (red lines) and change in transmission intensity at a specific time (blue lines) were estimated for each tested antibody using the maximum likelihood and the profile methods, respectively. P-values refer to the likelihood ratio tests for comparing the two reversible catalytic models

Fig. 4

Malaria positive cases reported from the two studied districts (1997–2015). Number of total malaria cases reported from Moneragala and Kurunegala districts during 1997–2015. Number of cases reported from 2005–2015 is indicated in the inset