Skip to main content
Top
Published in: Malaria Journal 1/2018

Open Access 01-12-2018 | Research

Subpatent malaria in a low transmission African setting: a cross-sectional study using rapid diagnostic testing (RDT) and loop-mediated isothermal amplification (LAMP) from Zambezi region, Namibia

Authors: Patrick McCreesh, Davis Mumbengegwi, Kathryn Roberts, Munyaradzi Tambo, Jennifer Smith, Brooke Whittemore, Gerard Kelly, Caitlin Moe, Max Murphy, Mukosha Chisenga, Bryan Greenhouse, Henry Ntuku, Immo Kleinschmidt, Hugh Sturrock, Petrina Uusiku, Roland Gosling, Adam Bennett, Michelle S. Hsiang

Published in: Malaria Journal | Issue 1/2018

Login to get access

Abstract

Background

Subpatent malaria infections, or low-density infections below the detection threshold of microscopy or standard rapid diagnostic testing (RDT), can perpetuate persistent transmission and, therefore, may be a barrier for countries like Namibia that are pursuing malaria elimination. This potential burden in Namibia has not been well characterized.

Methods

Using a two-stage cluster sampling, cross-sectional design, subjects of all age were enrolled during the end of the 2015 malaria transmission season in Zambezi region, located in northeast Namibia. Malaria RDTs were performed with subsequent gold standard testing by loop-mediated isothermal amplification (LAMP) using dried blood spots. Infection prevalence was measured and the diagnostic accuracy of RDT calculated. Relationships between recent fever, demographics, epidemiological factors, and infection were assessed.

Results

Prevalence of Plasmodium falciparum malaria infection was low: 0.8% (16/1919) by RDT and 2.2% (43/1919) by LAMP. All but one LAMP-positive infection was RDT-negative. Using LAMP as gold standard, the sensitivity and specificity of RDT were 2.3% and 99.2%, respectively. Compared to LAMP-negative infections, a higher portion LAMP-positive infections were associated with fever (45.2% vs. 30.4%, p = 0.04), though 55% of infections were not associated with fever. Agricultural occupations and cattle herding were significantly associated with LAMP-detectable infection (Adjusted ORs 5.02, 95% CI 1.77–14.23, and 11.82, 95% CI 1.06–131.81, respectively), while gender, travel, bed net use, and indoor residual spray coverage were not.

Conclusions

This study presents results from the first large-scale malaria cross-sectional survey from Namibia using molecular testing to characterize subpatent infections. Findings suggest that fever history and standard RDTs are not useful to address this burden. Achievement of malaria elimination may require active case detection using more sensitive point-of-care diagnostics or presumptive treatment and targeted to high-risk groups.
Appendix
Available only for authorised users
Literature
1.
go back to reference Tadesse FG, Pett H, Baidjoe A, Lanke K, Grignard L, Sutherland C, et al. Submicroscopic carriage of Plasmodium falciparum and Plasmodium vivax in a low endemic area in Ethiopia where no parasitaemia was detected by microscopy or rapid diagnostic test. Malar J. 2015;14:303.CrossRef Tadesse FG, Pett H, Baidjoe A, Lanke K, Grignard L, Sutherland C, et al. Submicroscopic carriage of Plasmodium falciparum and Plasmodium vivax in a low endemic area in Ethiopia where no parasitaemia was detected by microscopy or rapid diagnostic test. Malar J. 2015;14:303.CrossRef
2.
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.CrossRef 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.CrossRef
3.
go back to reference Wu L, van den Hoogen LL, Slater H, Walker PG, Ghani AC, Drakeley CJ, et al. Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies. Nature. 2015;528:S86–93.CrossRef Wu L, van den Hoogen LL, Slater H, Walker PG, Ghani AC, Drakeley CJ, et al. Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies. Nature. 2015;528:S86–93.CrossRef
4.
go back to reference Beshir KB, Sutherland CJ, Sawa P, Drakeley CJ, Okell L, Mweresa CK, et al. Residual Plasmodium falciparum parasitemia in Kenyan children after artemisinin-combination therapy is associated with increased transmission to mosquitoes and parasite recurrence. J Infect Dis. 2013;208:2017–24.CrossRef Beshir KB, Sutherland CJ, Sawa P, Drakeley CJ, Okell L, Mweresa CK, et al. Residual Plasmodium falciparum parasitemia in Kenyan children after artemisinin-combination therapy is associated with increased transmission to mosquitoes and parasite recurrence. J Infect Dis. 2013;208:2017–24.CrossRef
5.
go back to reference Tietje K, Hawkins K, Clerk C, Ebels K, McGray S, Crudder C, Okell L, et al. The essential role of infection-detection technologies for malaria elimination and eradication. Trends Parasitol. 2014;30:259–66.CrossRef Tietje K, Hawkins K, Clerk C, Ebels K, McGray S, Crudder C, Okell L, et al. The essential role of infection-detection technologies for malaria elimination and eradication. Trends Parasitol. 2014;30:259–66.CrossRef
6.
go back to reference Chen I, Clarke SE, Gosling R, Hamainza B, Killeen G, Magill A, et al. ‘Asymptomatic’ malaria: a chronic and debilitating infection that should be treated. PLoS Med. 2016;13:e1001942.CrossRef Chen I, Clarke SE, Gosling R, Hamainza B, Killeen G, Magill A, et al. ‘Asymptomatic’ malaria: a chronic and debilitating infection that should be treated. PLoS Med. 2016;13:e1001942.CrossRef
7.
go back to reference Cotter C, Sturrock HJW, Hsiang MS, Liu J, Phillips AA, Hwang J, et al. The changing epidemiology of malaria elimination: new strategies for new challenges. Lancet. 2013;382:900–11.CrossRef Cotter C, Sturrock HJW, Hsiang MS, Liu J, Phillips AA, Hwang J, et al. The changing epidemiology of malaria elimination: new strategies for new challenges. Lancet. 2013;382:900–11.CrossRef
8.
go back to reference Sturrock HJ, Novotny JM, Kunene S, Dlamini S, Zulu Z, Cohen JM, et al. Reactive case detection for malaria elimination: real-life experience from an ongoing program in Swaziland. PLoS One. 2013;8:e63830.CrossRef Sturrock HJ, Novotny JM, Kunene S, Dlamini S, Zulu Z, Cohen JM, et al. Reactive case detection for malaria elimination: real-life experience from an ongoing program in Swaziland. PLoS One. 2013;8:e63830.CrossRef
9.
go back to reference Wen S, Harvard KE, Gueye CS, Canavati SE, Chancellor A, Ahmed BN, et al. Targeting populations at higher risk for malaria: a survey of national malaria elimination programmes in the Asia Pacific. Malar J. 2016;15:271.CrossRef Wen S, Harvard KE, Gueye CS, Canavati SE, Chancellor A, Ahmed BN, et al. Targeting populations at higher risk for malaria: a survey of national malaria elimination programmes in the Asia Pacific. Malar J. 2016;15:271.CrossRef
10.
go back to reference Ministry of Health and Social Services. Malaria strategic plan (2010–2017). Windhoek: MOHSS; 2010. Ministry of Health and Social Services. Malaria strategic plan (2010–2017). Windhoek: MOHSS; 2010.
11.
go back to reference Government of the Republic of Namibia Ministry of Health and Social Services. Malaria indicator survey in Namibia Windhoek, Namibia; 2014. Government of the Republic of Namibia Ministry of Health and Social Services. Malaria indicator survey in Namibia Windhoek, Namibia; 2014.
12.
go back to reference Smith Gueye C, Gerigk M, Newby G, Lourenco C, Uusiku P, Liu J. Namibia’s path toward malaria elimination: a case study of malaria strategies and costs along the northern border. BMC Public Health. 2014;14:1190.CrossRef Smith Gueye C, Gerigk M, Newby G, Lourenco C, Uusiku P, Liu J. Namibia’s path toward malaria elimination: a case study of malaria strategies and costs along the northern border. BMC Public Health. 2014;14:1190.CrossRef
13.
go back to reference Government of the Republic of Namibia National Vector-borne Diseases Control Programme. Malaria annual report 2014/2015. Ministry of Health and Social Services, Republic of Namibia, Windhoek; 2015. Government of the Republic of Namibia National Vector-borne Diseases Control Programme. Malaria annual report 2014/2015. Ministry of Health and Social Services, Republic of Namibia, Windhoek; 2015.
14.
go back to reference Coetzee M, Craig M, le Sueur D. Distribution of African malaria mosquitoes belonging to the Anopheles gambiae complex. Parasitol Today. 2000;16:74–7.CrossRef Coetzee M, Craig M, le Sueur D. Distribution of African malaria mosquitoes belonging to the Anopheles gambiae complex. Parasitol Today. 2000;16:74–7.CrossRef
15.
go back to reference Government of the Republic of Namibia Statistics Agency: Zambezi 2011 Census Regional Profile Windhoek, Namibia; 2014. Government of the Republic of Namibia Statistics Agency: Zambezi 2011 Census Regional Profile Windhoek, Namibia; 2014.
16.
go back to reference Namibia Ministry of Health and Social Services: Namibia Demographic and Health Survey Windhoek, Namibia; 2013. Namibia Ministry of Health and Social Services: Namibia Demographic and Health Survey Windhoek, Namibia; 2013.
17.
go back to reference Gorstein J, Sullivan K, Parvanta I, Begin F. Indicators and methods for cross-sectional surveys of vitamin and mineral status of populations. CDC: Micronutrient Initiave; 2007. Gorstein J, Sullivan K, Parvanta I, Begin F. Indicators and methods for cross-sectional surveys of vitamin and mineral status of populations. CDC: Micronutrient Initiave; 2007.
18.
go back to reference Namibia Ministry of Health and Social Services. National policy on malaria. Windhoek; 2014. Namibia Ministry of Health and Social Services. National policy on malaria. Windhoek; 2014.
19.
go back to reference Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE. Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg. 1995;52:565–8.CrossRef Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE. Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg. 1995;52:565–8.CrossRef
20.
go back to reference Hopkins H, Gonzalez IJ, Polley SD, Angutoko P, Ategeka J, Asiimwe C, et al. Highly sensitive detection of malaria parasitemia in a malaria-endemic setting: performance of a new loop-mediated isothermal amplification kit in a remote clinic in Uganda. J Infect Dis. 2013;208:645–52.CrossRef Hopkins H, Gonzalez IJ, Polley SD, Angutoko P, Ategeka J, Asiimwe C, et al. Highly sensitive detection of malaria parasitemia in a malaria-endemic setting: performance of a new loop-mediated isothermal amplification kit in a remote clinic in Uganda. J Infect Dis. 2013;208:645–52.CrossRef
21.
go back to reference Steenkeste N, Incardona S, Chy S, Duval L, Ekala MT, Lim P, et al. Towards high-throughput molecular detection of Plasmodium: new approaches and molecular markers. Malar J. 2009;8:86.CrossRef Steenkeste N, Incardona S, Chy S, Duval L, Ekala MT, Lim P, et al. Towards high-throughput molecular detection of Plasmodium: new approaches and molecular markers. Malar J. 2009;8:86.CrossRef
22.
go back to reference West BT. Accounting for multi-stage sample designs in complex sample variance estimation Michigan program in survey methodology. Michigan: University of Michigan; 2014. West BT. Accounting for multi-stage sample designs in complex sample variance estimation Michigan program in survey methodology. Michigan: University of Michigan; 2014.
23.
go back to reference Kish L. Sampling organizations and groups of unequal sizes. Am Sociol Rev. 1965;30:564–72.CrossRef Kish L. Sampling organizations and groups of unequal sizes. Am Sociol Rev. 1965;30:564–72.CrossRef
24.
go back to reference Kulldorff M. A spatial scan statistic. Commun Statist Theory Methods. 1997;26:1481–96.CrossRef Kulldorff M. A spatial scan statistic. Commun Statist Theory Methods. 1997;26:1481–96.CrossRef
25.
go back to reference Bell D, Wongsrichanalai C, Barnwell JW. Ensuring quality and access for malaria diagnosis: how can it be achieved? Nat Rev Microbiol. 2006;4:S7–20.CrossRef Bell D, Wongsrichanalai C, Barnwell JW. Ensuring quality and access for malaria diagnosis: how can it be achieved? Nat Rev Microbiol. 2006;4:S7–20.CrossRef
26.
go back to reference WHO. Malaria rapid diagnostic test performance: summary results of WHO product testing of malaria RDTs: rounds 1–6 (2008–2015). Geneva: World Health Organization; 2008. WHO. Malaria rapid diagnostic test performance: summary results of WHO product testing of malaria RDTs: rounds 1–6 (2008–2015). Geneva: World Health Organization; 2008.
27.
go back to reference Parr JB, Verity R, Doctor SM, Janko M, Carey-Ewend K, Turman BJ, et al. Pfhrp2-deleted Plasmodium falciparum parasites in the Democratic Republic of the Congo: a national cross-sectional survey. J Infect Dis. 2017;216:36–44.CrossRef Parr JB, Verity R, Doctor SM, Janko M, Carey-Ewend K, Turman BJ, et al. Pfhrp2-deleted Plasmodium falciparum parasites in the Democratic Republic of the Congo: a national cross-sectional survey. J Infect Dis. 2017;216:36–44.CrossRef
28.
go back to reference Kozycki CT, Umulisa N, Rulisa S, Mwikarago EI, Musabyimana JP, Habimana JP, et al. False-negative malaria rapid diagnostic tests in Rwanda: impact of Plasmodium falciparum isolates lacking hrp2 and declining malaria transmission. Malar J. 2017;16:123.CrossRef Kozycki CT, Umulisa N, Rulisa S, Mwikarago EI, Musabyimana JP, Habimana JP, et al. False-negative malaria rapid diagnostic tests in Rwanda: impact of Plasmodium falciparum isolates lacking hrp2 and declining malaria transmission. Malar J. 2017;16:123.CrossRef
29.
go back to reference Dalrymple U, Arambepola R, Gething PW, Cameron E. How long do rapid diagnostic tests remain positive after anti-malarial treatment? Malar J. 2018;17:228.CrossRef Dalrymple U, Arambepola R, Gething PW, Cameron E. How long do rapid diagnostic tests remain positive after anti-malarial treatment? Malar J. 2018;17:228.CrossRef
30.
go back to reference Zaw MT, Thant M, Hlaing TM, Aung NZ, Thu M, Phumchuea K, et al. Asymptomatic and sub-microscopic malaria infection in Kayah State, eastern Myanmar. Malar J. 2017;16:138.CrossRef Zaw MT, Thant M, Hlaing TM, Aung NZ, Thu M, Phumchuea K, et al. Asymptomatic and sub-microscopic malaria infection in Kayah State, eastern Myanmar. Malar J. 2017;16:138.CrossRef
31.
go back to reference Smith JL, Auala J, Haindongo E, Uusiku P, Gosling R, Kleinschmidt I, et al. Malaria risk in young male travellers but local transmission persists: a case-control study in low transmission Namibia. Malar J. 2017;16:70.CrossRef Smith JL, Auala J, Haindongo E, Uusiku P, Gosling R, Kleinschmidt I, et al. Malaria risk in young male travellers but local transmission persists: a case-control study in low transmission Namibia. Malar J. 2017;16:70.CrossRef
32.
go back to reference Ruktanonchai NW, DeLeenheer P, Tatem AJ, Alegana VA, Caughlin TT, Zu Erbach-Schoenberg E, et al. Identifying malaria transmission foci for elimination using human mobility data. PLoS Comput Biol. 2016;12:e1004846.CrossRef Ruktanonchai NW, DeLeenheer P, Tatem AJ, Alegana VA, Caughlin TT, Zu Erbach-Schoenberg E, et al. Identifying malaria transmission foci for elimination using human mobility data. PLoS Comput Biol. 2016;12:e1004846.CrossRef
33.
go back to reference Medzihradsky OF, Kleinschmidt I, Mumbengegwi D, Roberts KW, McCreesh P, Dufour MK, et al. Study protocol for a cluster randomised controlled factorial design trial to assess the effectiveness and feasibility of reactive focal mass drug administration and vector control to reduce malaria transmission in the low endemic setting of Namibia. BMJ Open. 2018;8:e019294.CrossRef Medzihradsky OF, Kleinschmidt I, Mumbengegwi D, Roberts KW, McCreesh P, Dufour MK, et al. Study protocol for a cluster randomised controlled factorial design trial to assess the effectiveness and feasibility of reactive focal mass drug administration and vector control to reduce malaria transmission in the low endemic setting of Namibia. BMJ Open. 2018;8:e019294.CrossRef
34.
go back to reference Lindblade KA, Steinhardt L, Samuels A, Kachur SP, Slutsker L. The silent threat: asymptomatic parasitemia and malaria transmission. Expert Rev Anti Infect Ther. 2013;11:623–39.CrossRef Lindblade KA, Steinhardt L, Samuels A, Kachur SP, Slutsker L. The silent threat: asymptomatic parasitemia and malaria transmission. Expert Rev Anti Infect Ther. 2013;11:623–39.CrossRef
35.
go back to reference Imwong M, Stepniewska K, Tripura R, Peto TJ, Lwin KM, Vihokhern B, et al. Numerical distributions of parasite densities during asymptomatic malaria. J Infect Dis. 2016;213:1322–9.CrossRef Imwong M, Stepniewska K, Tripura R, Peto TJ, Lwin KM, Vihokhern B, et al. Numerical distributions of parasite densities during asymptomatic malaria. J Infect Dis. 2016;213:1322–9.CrossRef
36.
go back to reference Polley SD, Gonzalez IJ, Mohamed D, Daly R, Bowers K, Watson J, et al. Clinical evaluation of a loop-mediated amplification kit for diagnosis of imported malaria. J Infect Dis. 2013;208:637–44.CrossRef Polley SD, Gonzalez IJ, Mohamed D, Daly R, Bowers K, Watson J, et al. Clinical evaluation of a loop-mediated amplification kit for diagnosis of imported malaria. J Infect Dis. 2013;208:637–44.CrossRef
37.
go back to reference Herdiana H, Cotter C, Coutrier FN, Zarlinda I, Zelman BW, Tirta YK, et al. Malaria risk factor assessment using active and passive surveillance data from Aceh Besar, Indonesia, a low endemic, malaria elimination setting with Plasmodium knowlesi, Plasmodium vivax, and Plasmodium falciparum. Malar J. 2016;15:468.CrossRef Herdiana H, Cotter C, Coutrier FN, Zarlinda I, Zelman BW, Tirta YK, et al. Malaria risk factor assessment using active and passive surveillance data from Aceh Besar, Indonesia, a low endemic, malaria elimination setting with Plasmodium knowlesi, Plasmodium vivax, and Plasmodium falciparum. Malar J. 2016;15:468.CrossRef
38.
go back to reference Tegegne B, Getie S, Lemma W, Mohon AN, Pillai DR. Performance of loop-mediated isothermal amplification (LAMP) for the diagnosis of malaria among malaria suspected pregnant women in Northwest Ethiopia. Malar J. 2017;16:34.CrossRef Tegegne B, Getie S, Lemma W, Mohon AN, Pillai DR. Performance of loop-mediated isothermal amplification (LAMP) for the diagnosis of malaria among malaria suspected pregnant women in Northwest Ethiopia. Malar J. 2017;16:34.CrossRef
Metadata
Title
Subpatent malaria in a low transmission African setting: a cross-sectional study using rapid diagnostic testing (RDT) and loop-mediated isothermal amplification (LAMP) from Zambezi region, Namibia
Authors
Patrick McCreesh
Davis Mumbengegwi
Kathryn Roberts
Munyaradzi Tambo
Jennifer Smith
Brooke Whittemore
Gerard Kelly
Caitlin Moe
Max Murphy
Mukosha Chisenga
Bryan Greenhouse
Henry Ntuku
Immo Kleinschmidt
Hugh Sturrock
Petrina Uusiku
Roland Gosling
Adam Bennett
Michelle S. Hsiang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2018
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-018-2626-5

Other articles of this Issue 1/2018

Malaria Journal 1/2018 Go to the issue