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Published in: Malaria Journal 1/2017

Open Access 01-12-2017 | Research

Submicroscopic Plasmodium prevalence in relation to malaria incidence in 20 villages in western Cambodia

Authors: Rupam Tripura, Thomas J. Peto, Christianne C. Veugen, Chea Nguon, Chan Davoeung, Nicola James, Mehul Dhorda, Richard J. Maude, Jureeporn Duanguppama, Krittaya Patumrat, Mallika Imwong, Lorenz von Seidlein, Martin P. Grobusch, Nicholas J. White, Arjen M. Dondorp

Published in: Malaria Journal | Issue 1/2017

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Abstract

Background

Cambodia has seen a marked reduction in the incidence of Plasmodium falciparum over the past decade without a corresponding decline in Plasmodium vivax incidence. It is unknown to what extent local transmission is sustained by a chain of clinical and sub-clinical infections or by continued re-introduction via migration. Using an ultrasensitive molecular technique, 20 villages in western Cambodia were surveyed to detect the low season prevalence of P. falciparum and P. vivax and local treatment records were reviewed.

Methods

During March to May 2015 cross-sectional surveys were conducted in 20 villages in Battambang, western Cambodia. Demographic and epidemiological data and venous blood samples were collected from 50 randomly selected adult volunteers in each village. Blood was tested for Plasmodium infections by rapid diagnostic test (RDT), microscopy and high volume (0.5 ml packed red blood cell) quantitative polymerase chain reaction (uPCR). Positive samples were analysed by nested PCR to determine the Plasmodium species. Malaria case records were collected from the Provincial Health Department and village malaria workers to determine incidence and migration status.

Results

Among the 1000 participants, 91 (9.1%) were positive for any Plasmodium infection by uPCR, seven (0.7%) by microscopy, and two (0.2%) by RDT. uPCR P. vivax prevalence was 6.6%, P. falciparum 0.7%, and undetermined Plasmodium species 1.8%. Being male (adjusted OR 2.0; 95% CI 1.2-3.4); being a young adult <30 years (aOR 2.1; 95% CI 1.3–3.4); recent forest travel (aOR 2.8; 95% CI 1.6–4.8); and, a history of malaria (aOR 5.2; 95% CI 2.5–10.7) were independent risk factors for parasitaemia. Of the clinical malaria cases diagnosed by village malaria workers, 43.9% (297/634) and 38.4% (201/523) were among migrants in 2013 and in 2014, respectively. Plasmodium vivax prevalence determined by uPCR significantly correlated with vivax malaria incidences in both 2014 and 2015 (p = 0.001 and 0.002, respectively), whereas no relationship was observed in falciparum malaria (p = 0.36 and p = 0.59, respectively).

Discussion

There was heterogeneity in the malaria parasite reservoir between villages, and Plasmodium prevalence correlated with subsequent malaria incidence. The association was attributable chiefly to P. vivax infections, which were nine-fold more prevalent than P. falciparum infections. In the absence of a radical cure with 8-aminoquinolines, P. vivax transmission will continue even as P. falciparum prevalence declines. Migration was associated with over a third of incident cases of clinical malaria.
Trial registration clinicaltrials.gov (NCT01872702). Registered 4 June 2013
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Literature
1.
go back to reference Maude RJ, Nguon C, Ly P, Bunkea T, Ngor P, Canavati de la Torre SE. Spatial and temporal epidemiology of clinical malaria in Cambodia 2004–2013. Malar J. 2014;13:385.CrossRefPubMedPubMedCentral Maude RJ, Nguon C, Ly P, Bunkea T, Ngor P, Canavati de la Torre SE. Spatial and temporal epidemiology of clinical malaria in Cambodia 2004–2013. Malar J. 2014;13:385.CrossRefPubMedPubMedCentral
2.
go back to reference Verdrager J. Epidemiology of the emergence and spread of drug-resistant falciparum malaria in South-East Asia and Australasia. J Trop Med Hyg. 1986;89:277–89.PubMed Verdrager J. Epidemiology of the emergence and spread of drug-resistant falciparum malaria in South-East Asia and Australasia. J Trop Med Hyg. 1986;89:277–89.PubMed
3.
go back to reference Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, et al. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med. 2008;359:2619–20.CrossRefPubMed Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, et al. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med. 2008;359:2619–20.CrossRefPubMed
4.
go back to reference Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009;361:455–67.CrossRefPubMedPubMedCentral Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009;361:455–67.CrossRefPubMedPubMedCentral
5.
go back to reference Amaratunga C, Sreng S, Suon S, Phelps ES, Stepniewska K, Lim P, et al. Artemisinin-resistant Plasmodium falciparum in Pursat Province, western Cambodia: a parasite clearance rate study. Lancet Infect Dis. 2012;12:851–8.CrossRefPubMedPubMedCentral Amaratunga C, Sreng S, Suon S, Phelps ES, Stepniewska K, Lim P, et al. Artemisinin-resistant Plasmodium falciparum in Pursat Province, western Cambodia: a parasite clearance rate study. Lancet Infect Dis. 2012;12:851–8.CrossRefPubMedPubMedCentral
6.
go back to reference Amaratunga C, Lim P, Suon S, Sreng S, Mao S, Sopha C, et al. Dihydroartemisinin–piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study. Lancet Infect Dis. 2016;16:357–65.CrossRefPubMed Amaratunga C, Lim P, Suon S, Sreng S, Mao S, Sopha C, et al. Dihydroartemisinin–piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study. Lancet Infect Dis. 2016;16:357–65.CrossRefPubMed
7.
go back to reference Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014;371:411–23.CrossRefPubMedPubMedCentral Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014;371:411–23.CrossRefPubMedPubMedCentral
9.
go back to reference Dondorp AM, Fairhurst RM, Slutsker L, Macarthur JR, Breman JG, Guerin PJ, et al. The threat of artemisinin-resistant malaria. N Engl J Med. 2011;365:1073–5.CrossRefPubMedPubMedCentral Dondorp AM, Fairhurst RM, Slutsker L, Macarthur JR, Breman JG, Guerin PJ, et al. The threat of artemisinin-resistant malaria. N Engl J Med. 2011;365:1073–5.CrossRefPubMedPubMedCentral
10.
go back to reference Maude RJ, Pontavornpinyo W, Saralamba S, Aguas R, Yeung S, Dondorp AM, et al. The last man standing is the most resistant: eliminating artemisinin-resistant malaria in Cambodia. Malar J. 2009;8:31.CrossRefPubMedPubMedCentral Maude RJ, Pontavornpinyo W, Saralamba S, Aguas R, Yeung S, Dondorp AM, et al. The last man standing is the most resistant: eliminating artemisinin-resistant malaria in Cambodia. Malar J. 2009;8:31.CrossRefPubMedPubMedCentral
11.
go back to reference Maude RJ, Socheat D, Nguon C, Saroth P, Dara P, Li G, et al. Optimising strategies for Plasmodium falciparum malaria elimination in Cambodia: primaquine, mass drug administration and artemisinin resistance. PLoS ONE. 2012;7:e37166.CrossRefPubMedPubMedCentral Maude RJ, Socheat D, Nguon C, Saroth P, Dara P, Li G, et al. Optimising strategies for Plasmodium falciparum malaria elimination in Cambodia: primaquine, mass drug administration and artemisinin resistance. PLoS ONE. 2012;7:e37166.CrossRefPubMedPubMedCentral
13.
go back to reference Imwong M, Nguyen TN, Tripura R, Peto TJ, Lee SJ, Lwin KM, et al. The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand-Myanmar border areas, Cambodia, and Vietnam. Malar J. 2015;14:381.CrossRefPubMedPubMedCentral Imwong M, Nguyen TN, Tripura R, Peto TJ, Lee SJ, Lwin KM, et al. The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand-Myanmar border areas, Cambodia, and Vietnam. Malar J. 2015;14:381.CrossRefPubMedPubMedCentral
14.
go back to reference Tripura R, Peto TJ, Chalk J, Lee SJ, Sirithiranont P, Nguon C, et al. Persistent Plasmodium falciparum and Plasmodium vivax infections in a western Cambodian population: implications for prevention, treatment and elimination strategies. Malar J. 2016;15:181.CrossRefPubMedPubMedCentral Tripura R, Peto TJ, Chalk J, Lee SJ, Sirithiranont P, Nguon C, et al. Persistent Plasmodium falciparum and Plasmodium vivax infections in a western Cambodian population: implications for prevention, treatment and elimination strategies. Malar J. 2016;15:181.CrossRefPubMedPubMedCentral
15.
go back to reference Imwong M, Hanchana S, Malleret B, Rénia L, Day NP, Dondorp A, et al. High throughput ultra-sensitive molecular techniques to quantity low density malaria parasitaemias. J Clin Microbiol. 2014;52:3303–9.CrossRefPubMedPubMedCentral Imwong M, Hanchana S, Malleret B, Rénia L, Day NP, Dondorp A, et al. High throughput ultra-sensitive molecular techniques to quantity low density malaria parasitaemias. J Clin Microbiol. 2014;52:3303–9.CrossRefPubMedPubMedCentral
16.
go back to reference Steenkeste N, Rogers WO, Okell L, Jeanne I, Incardona S, Duval L, et al. Sub-microscopic malaria cases and mixed malaria infection in a remote area of high malaria endemicity in Rattanakiri province, Cambodia: implication for malaria elimination. Malar J. 2010;9:108.CrossRefPubMedPubMedCentral Steenkeste N, Rogers WO, Okell L, Jeanne I, Incardona S, Duval L, et al. Sub-microscopic malaria cases and mixed malaria infection in a remote area of high malaria endemicity in Rattanakiri province, Cambodia: implication for malaria elimination. Malar J. 2010;9:108.CrossRefPubMedPubMedCentral
17.
go back to reference Okell LC, Ghani AC, Lyons E, Drakeley CJ. Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. J Infect Dis. 2009;200:1509–17.CrossRefPubMed Okell LC, Ghani AC, Lyons E, Drakeley CJ. Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. J Infect Dis. 2009;200:1509–17.CrossRefPubMed
18.
go back to reference Shekalaghe SA, Bousema JT, Kunei KK, Lushino P, Masokoto A, Wolters LR, et al. Submicroscopic Plasmodium falciparum gametocyte carriage is common in an area of low and seasonal transmission in Tanzania. Trop Med Int Health. 2007;12:547–53.CrossRefPubMed Shekalaghe SA, Bousema JT, Kunei KK, Lushino P, Masokoto A, Wolters LR, et al. Submicroscopic Plasmodium falciparum gametocyte carriage is common in an area of low and seasonal transmission in Tanzania. Trop Med Int Health. 2007;12:547–53.CrossRefPubMed
19.
go back to reference Bhumiratana A, Intarapuk A, Sorosjinda-Nunthawarasilp P, Maneekan P, Koyadun S. Border malaria associated with multidrug resistance on Thailand-Myanmar and Thailand-Cambodia borders: transmission dynamic, vulnerability, and surveillance. Biomed Res Int. 2013;2013:363417.CrossRefPubMedPubMedCentral Bhumiratana A, Intarapuk A, Sorosjinda-Nunthawarasilp P, Maneekan P, Koyadun S. Border malaria associated with multidrug resistance on Thailand-Myanmar and Thailand-Cambodia borders: transmission dynamic, vulnerability, and surveillance. Biomed Res Int. 2013;2013:363417.CrossRefPubMedPubMedCentral
20.
go back to reference Incardona S, Vong S, Chiv L, Lim P, Nhem S, Sem R, et al. Large-scale malaria survey in Cambodia: novel insights on species distribution and risk factors. Malar J. 2007;6:37.CrossRefPubMedPubMedCentral Incardona S, Vong S, Chiv L, Lim P, Nhem S, Sem R, et al. Large-scale malaria survey in Cambodia: novel insights on species distribution and risk factors. Malar J. 2007;6:37.CrossRefPubMedPubMedCentral
21.
go back to reference Sluydts V, Heng S, Coosemans M, Van Roey K, Gryseels C, Canier L, et al. Spatial clustering and risk factors of malaria infections in Ratanakiri Province, Cambodia. Malar J. 2014;13:387.CrossRefPubMedPubMedCentral Sluydts V, Heng S, Coosemans M, Van Roey K, Gryseels C, Canier L, et al. Spatial clustering and risk factors of malaria infections in Ratanakiri Province, Cambodia. Malar J. 2014;13:387.CrossRefPubMedPubMedCentral
22.
go back to reference Peto TJ, Kloprogge SE, Tripura R, Nguon C, Sanann N, Yok S, et al. History of malaria treatment as a predictor of subsequent subclinical parasitaemia: a cross-sectional survey and malaria case records from three villages in Pailin, western Cambodia. Malar J. 2016;15:240.CrossRefPubMedPubMedCentral Peto TJ, Kloprogge SE, Tripura R, Nguon C, Sanann N, Yok S, et al. History of malaria treatment as a predictor of subsequent subclinical parasitaemia: a cross-sectional survey and malaria case records from three villages in Pailin, western Cambodia. Malar J. 2016;15:240.CrossRefPubMedPubMedCentral
23.
go back to reference Song J, Socheat D, Tan B, Dara P, Deng C, Sokunthea S, et al. Rapid and effective malaria control in Cambodia through mass administration of artemisinin–piperaquine. Malar J. 2010;9:57.CrossRefPubMedPubMedCentral Song J, Socheat D, Tan B, Dara P, Deng C, Sokunthea S, et al. Rapid and effective malaria control in Cambodia through mass administration of artemisinin–piperaquine. Malar J. 2010;9:57.CrossRefPubMedPubMedCentral
25.
go back to reference Seidlein L, Dondorp A. Fighting fire with fire: mass antimalarial drug administrations in an era of antimalarial resistance. Expert Rev Anti Infect Ther. 2015;13:715–30.CrossRef Seidlein L, Dondorp A. Fighting fire with fire: mass antimalarial drug administrations in an era of antimalarial resistance. Expert Rev Anti Infect Ther. 2015;13:715–30.CrossRef
26.
go back to reference Phommasone K, Adhikari B, Henriques G, Pongvongsa T, Phongmany P, von Seidlein L, et al. Asymptomatic Plasmodium infections in 18 villages of southern Savannakhet Province, Lao PDR (Laos). Malar J. 2016;15:296.CrossRefPubMedPubMedCentral Phommasone K, Adhikari B, Henriques G, Pongvongsa T, Phongmany P, von Seidlein L, et al. Asymptomatic Plasmodium infections in 18 villages of southern Savannakhet Province, Lao PDR (Laos). Malar J. 2016;15:296.CrossRefPubMedPubMedCentral
Metadata
Title
Submicroscopic Plasmodium prevalence in relation to malaria incidence in 20 villages in western Cambodia
Authors
Rupam Tripura
Thomas J. Peto
Christianne C. Veugen
Chea Nguon
Chan Davoeung
Nicola James
Mehul Dhorda
Richard J. Maude
Jureeporn Duanguppama
Krittaya Patumrat
Mallika Imwong
Lorenz von Seidlein
Martin P. Grobusch
Nicholas J. White
Arjen M. Dondorp
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2017
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-017-1703-5

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