Skip to main content
Top
Published in: Malaria Journal 1/2015

Open Access 01-12-2015 | Research

The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand–Myanmar border areas, Cambodia, and Vietnam

Authors: Mallika Imwong, Thuy Nhien Nguyen, Rupam Tripura, Tom J. Peto, Sue J. Lee, Khin Maung Lwin, Preyanan Suangkanarat, Atthanee Jeeyapant, Benchawan Vihokhern, Klanarong Wongsaen, Dao Van Hue, Le Thanh Dong, Tam-Uyen Nguyen, Yoel Lubell, Lorenz von Seidlein, Mehul Dhorda, Cholrawee Promnarate, Georges Snounou, Benoit Malleret, Laurent Rénia, Lilly Keereecharoen, Pratap Singhasivanon, Pasathorn Sirithiranont, Jem Chalk, Chea Nguon, Tran Tinh Hien, Nicholas Day, Nicholas J. White, Arjen Dondorp, Francois Nosten

Published in: Malaria Journal | Issue 1/2015

Login to get access

Abstract

Background

The importance of the submicroscopic reservoir of Plasmodium infections for malaria elimination depends on its size, which is generally considered small in low transmission settings. The precise estimation of this reservoir requires more sensitive parasite detection methods. The prevalence of asymptomatic, sub-microscopic malaria was assessed by a sensitive, high blood volume quantitative real-time polymerase chain reaction method in three countries of the Greater Mekong Sub-region.

Methods

Cross-sectional surveys were conducted in three villages in western Cambodia, four villages along the Thailand–Myanmar border and four villages in southwest Vietnam. Malaria parasitaemia was assessed by Plasmodium falciparum/pan malaria rapid diagnostic tests (RDTs), microscopy and a high volume ultra-sensitive real-time polymerase chain reaction (HVUSqPCR: limit of detection 22 parasites/mL). All villagers older than 6 months were invited to participate.

Results

A census before the surveys identified 7355 residents in the study villages. Parasite prevalence was 224/5008 (4 %) by RDT, 229/5111 (5 %) by microscopy, and 988/4975 (20 %) when assessed by HVUSqPCR. Of these 164 (3 %) were infected with P. falciparum, 357 (7 %) with Plasmodium vivax, 56 (1 %) with a mixed infection, and 411 (8 %) had parasite densities that were too low for species identification. A history of fever, male sex, and age of 15 years or older were independently associated with parasitaemia in a multivariate regression model stratified by site.

Conclusion

Light microscopy and RDTs identified only a quarter of all parasitaemic participants. The asymptomatic Plasmodium reservoir is considerable, even in low transmission settings. Novel strategies are needed to eliminate this previously under recognized reservoir of malaria transmission.
Appendix
Available only for authorised users
Literature
1.
go back to reference Sturrock HJ, Hsiang MS, Cohen JM, Smith DL, Greenhouse B, Bousema T, et al. Targeting asymptomatic malaria infections: active surveillance in control and elimination. PLoS Med. 2013;10:e1001467.PubMedCentralCrossRefPubMed Sturrock HJ, Hsiang MS, Cohen JM, Smith DL, Greenhouse B, Bousema T, et al. Targeting asymptomatic malaria infections: active surveillance in control and elimination. PLoS Med. 2013;10:e1001467.PubMedCentralCrossRefPubMed
2.
go back to reference Wongsrichanalai C, Barcus MJ, Muth S, Sutamihardja A, Wernsdorfer WH. A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT). Am J Trop Med Hyg. 2007;77:119–27.PubMed Wongsrichanalai C, Barcus MJ, Muth S, Sutamihardja A, Wernsdorfer WH. A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT). Am J Trop Med Hyg. 2007;77:119–27.PubMed
3.
go back to reference McNamara DT, Kasehagen LJ, Grimberg BT, Cole-Tobian J, Collins WE, Zimmerman PA. Diagnosing infection levels of four human malaria parasite species by a polymerase chain reaction/ligase detection reaction fluorescent microsphere-based assay. Am J Trop Med Hyg. 2006;74:413–21.PubMedCentralPubMed McNamara DT, Kasehagen LJ, Grimberg BT, Cole-Tobian J, Collins WE, Zimmerman PA. Diagnosing infection levels of four human malaria parasite species by a polymerase chain reaction/ligase detection reaction fluorescent microsphere-based assay. Am J Trop Med Hyg. 2006;74:413–21.PubMedCentralPubMed
4.
go back to reference Snounou G, Viriyakosol S, Zhu XP, Jarra W, Pinheiro L, do Rosario VE, et al. High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction. Mol Biochem Parasitol. 1993;61:315–20. Snounou G, Viriyakosol S, Zhu XP, Jarra W, Pinheiro L, do Rosario VE, et al. High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction. Mol Biochem Parasitol. 1993;61:315–20.
5.
go back to reference Imwong M, Hanchana S, Malleret B, Renia L, Day NP, Dondorp A, et al. High throughput ultra-sensitive molecular techniques to quantify low density malaria parasitaemias. J Clin Microbiol. 2014;9:3003–9. Imwong M, Hanchana S, Malleret B, Renia L, Day NP, Dondorp A, et al. High throughput ultra-sensitive molecular techniques to quantify low density malaria parasitaemias. J Clin Microbiol. 2014;9:3003–9.
6.
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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
7.
go back to reference Childs DZ, Cattadori IM, Suwonkerd W, Prajakwong S, Boots M. Spatiotemporal patterns of malaria incidence in northern Thailand. Trans R Soc Trop Med Hyg. 2006;100:623–31.CrossRefPubMed Childs DZ, Cattadori IM, Suwonkerd W, Prajakwong S, Boots M. Spatiotemporal patterns of malaria incidence in northern Thailand. Trans R Soc Trop Med Hyg. 2006;100:623–31.CrossRefPubMed
8.
go back to reference Maude RJ, Hasan MU, Hossain MA, Sayeed AA, Kanti Paul S, Rahman W, Maude RR, Vaid N, Ghose A, Amin R, et al. Temporal trends in severe malaria in Chittagong, Bangladesh. Malar J. 2012;11:323. Maude RJ, Hasan MU, Hossain MA, Sayeed AA, Kanti Paul S, Rahman W, Maude RR, Vaid N, Ghose A, Amin R, et al. Temporal trends in severe malaria in Chittagong, Bangladesh. Malar J. 2012;11:323.
9.
10.
go back to reference Carrara VI, Lwin KM, Phyo AP, Ashley E, Wiladphaingern J, Sriprawat K, et al. Malaria burden and artemisinin resistance in the mobile and migrant population on the Thai–Myanmar border, 1999–2011: an observational study. PLoS Med. 2013;10:e1001398.PubMedCentralCrossRefPubMed Carrara VI, Lwin KM, Phyo AP, Ashley E, Wiladphaingern J, Sriprawat K, et al. Malaria burden and artemisinin resistance in the mobile and migrant population on the Thai–Myanmar border, 1999–2011: an observational study. PLoS Med. 2013;10:e1001398.PubMedCentralCrossRefPubMed
11.
go back to reference Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014;371:411–23.PubMedCentralCrossRefPubMed Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014;371:411–23.PubMedCentralCrossRefPubMed
12.
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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
13.
go back to reference Thanh NV, Toan TQ, Cowman AF, Casey GJ, Phuc BQ, Tien NT. Monitoring for Plasmodium falciparum drug resistance to artemisinin and artesunate in Binh Phuoc Province, Vietnam: 1998–2009. Malar J. 2010;9:181.PubMedCentralCrossRefPubMed Thanh NV, Toan TQ, Cowman AF, Casey GJ, Phuc BQ, Tien NT. Monitoring for Plasmodium falciparum drug resistance to artemisinin and artesunate in Binh Phuoc Province, Vietnam: 1998–2009. Malar J. 2010;9:181.PubMedCentralCrossRefPubMed
14.
go back to reference Imwong M, Hanchana S, Malleret B, Rénia L, Day NP, Dondorp A. High throughput ultra-sensitive molecular techniques to quantity low density malaria parasitaemias. J Clin Microbiol. 2014;52(9):3303–9.PubMedCentralCrossRefPubMed Imwong M, Hanchana S, Malleret B, Rénia L, Day NP, Dondorp A. High throughput ultra-sensitive molecular techniques to quantity low density malaria parasitaemias. J Clin Microbiol. 2014;52(9):3303–9.PubMedCentralCrossRefPubMed
15.
go back to reference Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM. 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. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med. 2008;359:2619–20.CrossRefPubMed
16.
go back to reference WHO. World malaria report 2012. Geneva: World Health Organization; 2012. WHO. World malaria report 2012. Geneva: World Health Organization; 2012.
17.
go back to reference WHO. Global plan for artemisinin resistance containment. Geneva: World Health Organization; 2012. WHO. Global plan for artemisinin resistance containment. Geneva: World Health Organization; 2012.
18.
go back to reference WHO. Emergency response plan to artemisinin resistance in the Greater Mekong Subregion. Geneva: World Health Organization; 2013. WHO. Emergency response plan to artemisinin resistance in the Greater Mekong Subregion. Geneva: World Health Organization; 2013.
19.
go back to reference Hoyer S, Nguon S, Kim S, Habib N, Khim N, Sum S, et al. Focused screening and treatment (FSAT): a PCR-based strategy to detect malaria parasite carriers and contain drug resistant P. falciparum, Pailin, Cambodia. PLoS One. 2012;7:e45797.PubMedCentralCrossRefPubMed Hoyer S, Nguon S, Kim S, Habib N, Khim N, Sum S, et al. Focused screening and treatment (FSAT): a PCR-based strategy to detect malaria parasite carriers and contain drug resistant P. falciparum, Pailin, Cambodia. PLoS One. 2012;7:e45797.PubMedCentralCrossRefPubMed
20.
go back to reference Cook J, Speybroeck N, Sochanta T, Somony H, Sokny M, Claes F, et al. Sero-epidemiological evaluation of changes in Plasmodium falciparum and Plasmodium vivax transmission patterns over the rainy season in Cambodia. Malar J. 2012;11:86.PubMedCentralCrossRefPubMed Cook J, Speybroeck N, Sochanta T, Somony H, Sokny M, Claes F, et al. Sero-epidemiological evaluation of changes in Plasmodium falciparum and Plasmodium vivax transmission patterns over the rainy season in Cambodia. Malar J. 2012;11:86.PubMedCentralCrossRefPubMed
21.
go back to reference Hien TT, Thuy-Nhien NT, Phu NH, Boni MF, Thanh NV, Nha-Ca NT, et al. In vivo susceptibility of Plasmodium falciparum to artesunate in Binh Phuoc Province, Vietnam. Malar J. 2012;11:355.PubMedCentralCrossRefPubMed Hien TT, Thuy-Nhien NT, Phu NH, Boni MF, Thanh NV, Nha-Ca NT, et al. In vivo susceptibility of Plasmodium falciparum to artesunate in Binh Phuoc Province, Vietnam. Malar J. 2012;11:355.PubMedCentralCrossRefPubMed
22.
go back to reference Kamau E, Tolbert LS, Kortepeter L, Pratt M, Nyakoe N, Muringo L, et al. Development of a highly sensitive genus-specific quantitative reverse transcriptase real-time PCR assay for detection and quantitation of plasmodium by amplifying RNA and DNA of the 18S rRNA genes. J Clin Microbiol. 2011;49:2946–53.PubMedCentralCrossRefPubMed Kamau E, Tolbert LS, Kortepeter L, Pratt M, Nyakoe N, Muringo L, et al. Development of a highly sensitive genus-specific quantitative reverse transcriptase real-time PCR assay for detection and quantitation of plasmodium by amplifying RNA and DNA of the 18S rRNA genes. J Clin Microbiol. 2011;49:2946–53.PubMedCentralCrossRefPubMed
23.
go back to reference Imwong M, Snounou G, Pukrittayakamee S, Tanomsing N, Kim JR, Nandy A, et al. Relapses of Plasmodium vivax infection usually result from activation of heterologous hypnozoites. J Infect Dis. 2007;195:927–33.CrossRefPubMed Imwong M, Snounou G, Pukrittayakamee S, Tanomsing N, Kim JR, Nandy A, et al. Relapses of Plasmodium vivax infection usually result from activation of heterologous hypnozoites. J Infect Dis. 2007;195:927–33.CrossRefPubMed
24.
go back to reference Snounou G. Detection and identification of the four malaria parasite species infecting humans by PCR amplification. Methods Mol Biol. 1996;50:263–91.PubMed Snounou G. Detection and identification of the four malaria parasite species infecting humans by PCR amplification. Methods Mol Biol. 1996;50:263–91.PubMed
25.
go back to reference Bousema T, Drakeley C. Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination. Clin Microbiol Rev. 2011;24:377–410.PubMedCentralCrossRefPubMed Bousema T, Drakeley C. Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination. Clin Microbiol Rev. 2011;24:377–410.PubMedCentralCrossRefPubMed
26.
go back to reference Okell LC, Bousema T, Griffin JT, Ouedraogo AL, Ghani AC, Drakeley CJ. Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat Commun. 2012;3:1237.PubMedCentralCrossRefPubMed Okell LC, Bousema T, Griffin JT, Ouedraogo AL, Ghani AC, Drakeley CJ. Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat Commun. 2012;3:1237.PubMedCentralCrossRefPubMed
27.
go back to reference Joice R, Nilsson SK, Montgomery J, Dankwa S, Egan E, Morahan B, et al. Plasmodium falciparum transmission stages accumulate in the human bone marrow. Sci Transl Med. 2014;6:244re245. Joice R, Nilsson SK, Montgomery J, Dankwa S, Egan E, Morahan B, et al. Plasmodium falciparum transmission stages accumulate in the human bone marrow. Sci Transl Med. 2014;6:244re245.
28.
go back to reference Anderson TJ, Haubold B, Williams JT, Estrada-Franco JG, Richardson L, Mollinedo R, et al. Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum. Mol Biol Evol. 2000;17:1467–82.CrossRefPubMed Anderson TJ, Haubold B, Williams JT, Estrada-Franco JG, Richardson L, Mollinedo R, et al. Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum. Mol Biol Evol. 2000;17:1467–82.CrossRefPubMed
29.
go back to reference Collins WE, Jeffery GM. A retrospective examination of secondary sporozoite- and trophozoite-induced infections with Plasmodium falciparum: development of parasitologic and clinical immunity following secondary infection. Am J Trop Med Hyg. 1999;61:20–35.CrossRefPubMed Collins WE, Jeffery GM. A retrospective examination of secondary sporozoite- and trophozoite-induced infections with Plasmodium falciparum: development of parasitologic and clinical immunity following secondary infection. Am J Trop Med Hyg. 1999;61:20–35.CrossRefPubMed
30.
go back to reference Jeffery GM, Eyles DE. The duration in the human host of infections with a Panama strain of Plasmodium falciparum. Am J Trop Med Hyg. 1954;3:219–24.PubMed Jeffery GM, Eyles DE. The duration in the human host of infections with a Panama strain of Plasmodium falciparum. Am J Trop Med Hyg. 1954;3:219–24.PubMed
31.
go back to reference Eyles DE, Young MD. The duration of untreated or inadequately treated Plasmodium falciparum infections in the human host. J Natl Malar Soc. 1951;10:327–36.PubMed Eyles DE, Young MD. The duration of untreated or inadequately treated Plasmodium falciparum infections in the human host. J Natl Malar Soc. 1951;10:327–36.PubMed
32.
go back to reference von Seidlein L. The failure of screening and treating as a malaria elimination strategy. PLoS Med. 2014;11:e1001595.CrossRef von Seidlein L. The failure of screening and treating as a malaria elimination strategy. PLoS Med. 2014;11:e1001595.CrossRef
Metadata
Title
The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand–Myanmar border areas, Cambodia, and Vietnam
Authors
Mallika Imwong
Thuy Nhien Nguyen
Rupam Tripura
Tom J. Peto
Sue J. Lee
Khin Maung Lwin
Preyanan Suangkanarat
Atthanee Jeeyapant
Benchawan Vihokhern
Klanarong Wongsaen
Dao Van Hue
Le Thanh Dong
Tam-Uyen Nguyen
Yoel Lubell
Lorenz von Seidlein
Mehul Dhorda
Cholrawee Promnarate
Georges Snounou
Benoit Malleret
Laurent Rénia
Lilly Keereecharoen
Pratap Singhasivanon
Pasathorn Sirithiranont
Jem Chalk
Chea Nguon
Tran Tinh Hien
Nicholas Day
Nicholas J. White
Arjen Dondorp
Francois Nosten
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2015
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-015-0906-x

Other articles of this Issue 1/2015

Malaria Journal 1/2015 Go to the issue