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Malaria Journal
Published in: Malaria Journal 1/2021

Open Access 01-12-2021 | Plasmodium Falciparum | Research

The epidemiology and detectability of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in low, moderate and high transmission settings in Ethiopia

Authors: Elifaged Hailemeskel, Surafel K Tebeje, Sinknesh W. Behaksra, Girma Shumie, Getasew Shitaye, Migbaru Keffale, Wakweya Chali, Abrham Gashaw, Temesgen Ashine, Chris Drakeley, Teun Bousema, Endalamaw Gadisa, Fitsum G. Tadesse

Published in: Malaria Journal | Issue 1/2021

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Abstract

Background

As countries move to malaria elimination, detecting and targeting asymptomatic malaria infections might be needed. Here, the epidemiology and detectability of asymptomatic Plasmodium falciparum and Plasmodium vivax infections were investigated in different transmission settings in Ethiopia.

Method:

A total of 1093 dried blood spot (DBS) samples were collected from afebrile and apparently healthy individuals across ten study sites in Ethiopia from 2016 to 2020. Of these, 862 were from community and 231 from school based cross-sectional surveys. Malaria infection status was determined by microscopy or rapid diagnostics tests (RDT) and 18S rRNA-based nested PCR (nPCR). The annual parasite index (API) was used to classify endemicity as low (API > 0 and < 5), moderate (API ≥ 5 and < 100) and high transmission (API ≥ 100) and detectability of infections was assessed in these settings.

Results

In community surveys, the overall prevalence of asymptomatic Plasmodium infections by microscopy/RDT, nPCR and all methods combined was 12.2% (105/860), 21.6% (183/846) and 24.1% (208/862), respectively. The proportion of nPCR positive infections that was detectable by microscopy/RDT was 48.7% (73/150) for P. falciparum and 4.6% (2/44) for P. vivax. Compared to low transmission settings, the likelihood of detecting infections by microscopy/RDT was increased in moderate (Adjusted odds ratio [AOR]: 3.4; 95% confidence interval [95% CI] 1.6–7.2, P = 0.002) and high endemic settings (AOR = 5.1; 95% CI 2.6–9.9, P < 0.001). After adjustment for site and correlation between observations from the same survey, the likelihood of detecting asymptomatic infections by microscopy/RDT (AOR per year increase = 0.95, 95% CI 0.9–1.0, P = 0.013) declined with age.

Conclusions

Conventional diagnostics missed nearly half of the asymptomatic Plasmodium reservoir detected by nPCR. The detectability of infections was particularly low in older age groups and low transmission settings. These findings highlight the need for sensitive diagnostic tools to detect the entire parasite reservoir and potential infection transmitters.
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Literature
1.
2.
Taffese HS, Hemming-Schroeder E, Koepfli C, Tesfaye G, Lee M-c, Kazura J, Yan G-Y, Zhou G-F. Malaria epidemiology and interventions in Ethiopia from 2001 to 2016. Infect Dis Poverty. 2018;7:1–9.CrossRef
3.
4.
5.
6.
Mwesigwa J, Achan J, Di Tanna GL, Affara M, Jawara M, Worwui A, Hamid-Adiamoh M, Kanuteh F, Ceesay S, Bousema T. Residual malaria transmission dynamics varies across The Gambia despite high coverage of control interventions. PLoS One. 2017;12(11):e0187059.PubMedPubMedCentralCrossRef
7.
Thwing J, Camara A, Candrinho B, Zulliger R, Colborn J, Painter J, Plucinski MM. A robust estimator of malaria incidence from routine health facility data. Am J Tropical Med Hyg. 2020;102(4):811–20.CrossRef
8.
Weiss DJ, Lucas TC, Nguyen M, Nandi AK, Bisanzio D, Battle KE, Cameron E, Twohig KA, Pfeffer DA, Rozier JA. Mapping the global prevalence, incidence, and mortality of Plasmodium falciparum, 2000–17: a spatial and temporal modelling study. Lancet. 2019;394(10195):322–31.PubMedPubMedCentralCrossRef
9.
Bousema T, Okell L, Felger I, Drakeley C. Asymptomatic malaria infections: detectability, transmissibility and public health relevance. Nat Rev Microbiol. 2014;12(12):833–40.PubMedCrossRef
10.
Cheaveau J, Mogollon DC, Mohon MAN, Golassa L, Yewhalaw D, Pillai DR. Asymptomatic malaria in the clinical and public health context. Expert Rev Anti Infect Ther. 2019;17(12):997–1010.PubMedCrossRef
11.
Whittaker C, Slater HC, Bousema T, Drakeley C, Ghani A, Okell LC. Variation in the Prevalence of Submicroscopic Malaria Infections: Historical Transmission Intensity and Age as Key Determinants. bioRxiv. 2019:554311.
12.
Ouedraogo AL, Goncalves BP, Gneme A, Wenger EA, Guelbeogo MW, Ouedraogo A, Gerardin J, Bever CA, Lyons H, Pitroipa X, et al. Dynamics of the Human Infectious Reservoir for Malaria Determined by Mosquito Feeding Assays and Ultrasensitive Malaria Diagnosis in Burkina Faso. J Infect Dis. 2016;213(1):90–9.PubMedCrossRef
13.
Gonçalves BP, Kapulu MC, Sawa P, Guelbéogo WM, Tiono AB, Grignard L, Stone W, Hellewell J, Lanke K, Bastiaens GJH, et al. Examining the human infectious reservoir for Plasmodium falciparum malaria in areas of differing transmission intensity. Nat Commun. 2017;8(1):1133.PubMedPubMedCentralCrossRef
14.
Tadesse FG, Slater HC, Chali W, Teelen K, Lanke K, Belachew M, Menberu T, Shumie G, Shitaye G, Okell LC, et al. The relative contribution of symptomatic and asymptomatic Plasmodium vivax and Plasmodium falciparum infections to the infectious reservoir in a low-endemic setting in Ethiopia. Clin Infect Dis. 2018;66(12):1883–91.PubMedCrossRef
15.
Slater HC, Ross A, Felger I, Hofmann NE, Robinson L, Cook J, Goncalves BP, Bjorkman A, Ouedraogo AL, Morris U, et al. The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density. Nat Commun. 2019;10(1):1433.PubMedPubMedCentralCrossRef
16.
Tadesse FG, Pett H, Baidjoe A, Lanke K, Grignard L, Sutherland C, Hall T, Drakeley C, Bousema T, Mamo H. 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.PubMedPubMedCentralCrossRef
17.
Zhou G, Yewhalaw D, Lo E, Zhong D, Wang X, Degefa T, Zemene E, Lee M-c, Kebede E, Tushune K, Yan G. Analysis of asymptomatic and clinical malaria in urban and suburban settings of southwestern Ethiopia in the context of sustaining malaria control and approaching elimination. Malar J. 2016;15(1):1–9.CrossRef
18.
Assefa A, Ahmed AA, Deressa W, Wilson GG, Kebede A, Mohammed H, Sassine M, Haile M, Dilu D, Teka H. Assessment of subpatent Plasmodium infection in northwestern Ethiopia. Malar J. 2020;19:1–10.CrossRef
19.
Golassa L, Enweji N, Erko B, Aseffa A, Swedberg G. Detection of a substantial number of sub-microscopic Plasmodium falciparum infections by polymerase chain reaction: a potential threat to malaria control and diagnosis in Ethiopia. Malar J. 2013;12:8.CrossRef
20.
21.
Tadesse FG, Hoogen L, Lanke K, Schildkraut J, Tetteh K, Aseffa A, Mamo H, Sauerwein R, Felger I, Drakeley C. The shape of the iceberg: quantification of submicroscopic Plasmodium falciparum and Plasmodium vivax parasitaemia and gametocytaemia in five low endemic settings in Ethiopia. Malar J. 2017;16(1):99.PubMedPubMedCentralCrossRef
22.
Brooker S, Kolaczinski JH, Gitonga CW, Noor AM, Snow RW. The use of schools for malaria surveillance and programme evaluation in Africa. Malar J. 2009;8(1):231.PubMedPubMedCentralCrossRef
23.
24.
Baidjoe A, Stone W, Ploemen I, Shagari S, Grignard L, Osoti V, Makori E, Stevenson J, Kariuki S, Sutherland C. Combined DNA extraction and antibody elution from filter papers for the assessment of malaria transmission intensity in epidemiological studies. Malar J. 2013;12(1):272.PubMedPubMedCentralCrossRef
25.
Snounou G, Viriyakosol S, Zhu XP, Jarra W, Pinheiro L, do Rosario VE, Thaithong S, Brown KN. High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction. Mol Biochem Parasitol. 1993;61(2):315–20.PubMedCrossRef
26.
Adebo SM, Eckerle JK, Andrews ME, Howard CR, John CC. Asymptomatic Malaria and Other Infections in Children Adopted from Ethiopia, United States, 2006–2011. Emerg Infect Dis. 2015;21(7):1227–9.PubMedPubMedCentralCrossRef
27.
Alemu G, Mama M. Assessing ABO/Rh blood group frequency and association with asymptomatic malaria among blood donors attending Arba Minch blood bank, South Ethiopia. Malar Res Treat. 2016;2016:8043768.PubMed
28.
Fekadu M, Yenit MK, Lakew AM. The prevalence of asymptomatic malaria parasitemia and associated factors among adults in Dembia district, northwest Ethiopia, 2017. Arch Public Health. 2018;76(1):74.PubMedPubMedCentralCrossRef
29.
Nega D, Dana D, Tefera T, Eshetu T. Prevalence and predictors of asymptomatic malaria parasitemia among pregnant women in the rural surroundings of Arbaminch Town, South Ethiopia. PLoS One. 2015;10(4):e0123630.PubMedPubMedCentralCrossRef
30.
Worku L, Damtie D, Endris M, Getie S, Aemero M. Asymptomatic Malaria and Associated Risk Factors among School Children in Sanja Town. Northwest Ethiopia Int Sch Res Notices. 2014;2014:303269.PubMed
31.
Aschale Y, Mengist A, Bitew A, Kassie B, Talie A. Prevalence of malaria and associated risk factors among asymptomatic migrant laborers in West Armachiho District, Northwest Ethiopia. Res Rep Trop Med. 2018;9:95–101.PubMedPubMedCentral
32.
Lo E, Yewhalaw D, Zhong D, Zemene E, Degefa T, Tushune K, Ha M, Lee MC, James AA, Yan G. Molecular epidemiology of Plasmodium vivax and Plasmodium falciparum malaria among Duffy-positive and Duffy-negative populations in Ethiopia. Malar J. 2015;14:84.PubMedPubMedCentralCrossRef
33.
Golassa L, Baliraine FN, Enweji N, Erko B, Swedberg G, Aseffa A. Microscopic and molecular evidence of the presence of asymptomatic Plasmodium falciparum and Plasmodium vivax infections in an area with low, seasonal and unstable malaria transmission in Ethiopia. BMC Infect Dis. 2015;15:310.PubMedPubMedCentralCrossRef
34.
Girma S, Cheaveau J, Mohon AN, Marasinghe D, Legese R, Balasingam N, Abera A, Feleke SM, Golassa L, Pillai DR. Prevalence and epidemiological characteristics of asymptomatic malaria based on ultrasensitive diagnostics: a cross-sectional study. Clin Infect Dis. 2019;69(6):1003–10.PubMedCrossRef
35.
Santana-Morales MA, Afonso-Lehmann RN, Quispe MA, Reyes F, Berzosa P, Benito A, Valladares B, Martinez-Carretero E. Microscopy and molecular biology for the diagnosis and evaluation of malaria in a hospital in a rural area of Ethiopia. Malar J. 2012;11:199.PubMedPubMedCentralCrossRef
36.
Okell LC, Bousema T, Griffin JT, Ouédraogo AL, Ghani AC, Drakeley CJ. Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat commun. 2012;3:1237.PubMedCrossRef
37.
Wu L, van den Hoogen LL, Slater H, Walker PGT, Ghani AC, Drakeley CJ, Okell LC. Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies. Nature. 2015;528:86–93.CrossRef
38.
Idris ZM, Chan CW, Kongere J, Gitaka J, Logedi J, Omar A, Obonyo C, Machini BK, Isozumi R, Teramoto I. High and heterogeneous prevalence of asymptomatic and sub-microscopic malaria infections on islands in Lake Victoria, Kenya. Sci Rep. 2016;6:36958.PubMedPubMedCentralCrossRef
39.
Berzosa P, de Lucio A, Romay-Barja M, Herrador Z, González V, García L, Fernández-Martínez A, Santana-Morales M, Ncogo P, Valladares B. Comparison of three diagnostic methods (microscopy, RDT, and PCR) for the detection of malaria parasites in representative samples from Equatorial Guinea. Malar J. 2018;17:333.PubMedPubMedCentralCrossRef
40.
Whittaker C, Slater H, Bousema T, Drakeley C, Ghani A, Okell L: Global & Temporal Patterns of Submicroscopic Plasmodium falciparum Malaria Infection. bioRxiv. 2020:554311.
41.
Sattabongkot J, Suansomjit C, Nguitragool W, Sirichaisinthop J, Warit S, Tiensuwan M, Buates S. Prevalence of asymptomatic Plasmodium infections with sub-microscopic parasite densities in the northwestern border of Thailand: a potential threat to malaria elimination. Malar J. 2018;17(1):329.PubMedPubMedCentralCrossRef
42.
Clark EH, Silva CJ, Weiss GE, Li S, Padilla C, Crompton PD, Hernandez JN, Branch OH. Plasmodium falciparum malaria in the Peruvian Amazon, a region of low transmission, is associated with immunologic memory. Infect Immun. 2012;80:1583–92.PubMedPubMedCentralCrossRef
43.
Proietti C, Pettinato DD, Kanoi BN, Ntege E, Crisanti A, Riley EM, Egwang TG, Drakeley C, Bousema T. Continuing intense malaria transmission in northern Uganda. Am J Tropical Med Hyg. 2011;84(5):830–7.CrossRef
44.
Koepfli C, Robinson LJ, Rarau P, Salib M, Sambale N, Wampfler R, Betuela I, Nuitragool W, Barry AE, Siba P, et al. Blood-stage parasitaemia and age determine Plasmodium falciparum and P. vivax gametocytaemia in Papua New Guinea. PLoS One. 2015;10(5):e0126747.PubMedPubMedCentralCrossRef
45.
Hofmann NE, Karl S, Wampfler R, Kiniboro B, Teliki A, Iga J, Waltmann A, Betuela I, Felger I, Robinson LJ, Mueller I. The complex relationship of exposure to new Plasmodium infections and incidence of clinical malaria in Papua New Guinea. eLife. 2017;6:e23708.PubMedPubMedCentralCrossRef
46.
Lim C, Pereira L, Saliba KS, Mascarenhas A, Maki JN, Chery L, Gomes E, Rathod PK, Duraisingh MT. Reticulocyte Preference and Stage Development of Plasmodium vivax Isolates. J Infect Dis. 2016;214(7):1081–4.PubMedPubMedCentralCrossRef
47.
Moreno-Pérez DA, Ruíz JA, Patarroyo MA. Reticulocytes: Plasmodium vivax target cells. Biol Cell. 2013;105(6):251–60.PubMedCrossRef
48.
49.
Bell DR, Wilson DW, Martin LB. False-positive results of a Plasmodium falciparum histidine-rich protein 2–detecting malaria rapid diagnostic test due to high sensitivity in a community with fluctuating low parasite density. Am J Tropical Med Hyg. 2005;73(1):199–203.CrossRef
50.
Dalrymple U, Arambepola R, Gething PW, Cameron E. How long do rapid diagnostic tests remain positive after anti-malarial treatment? Malar J. 2018;17(1):228.PubMedPubMedCentralCrossRef
51.
Males S, Gaye O, Garcia A. Long-term asymptomatic carriage of Plasmodium falciparum protects from malaria attacks: a prospective study among Senegalese children. Clin Infect Dis. 2008;46(4):516–22.PubMedCrossRef
52.
Nguyen T-N, von Seidlein L, Nguyen T-V, Truong P-N, Hung SD, Pham H-T, Nguyen T-U, Le TD, Dao VH, Mukaka M, et al. The persistence and oscillations of submicroscopic Plasmodium falciparum and Plasmodium vivax infections over time in Vietnam: an open cohort study. Lancet Infect Dis. 2018;18(5):565–72.PubMedPubMedCentralCrossRef
53.
Tripura R, Peto TJ, Chalk J, Lee SJ, Sirithiranont P, Nguon C, Dhorda M, von Seidlein L, Maude RJ, Day NPJ, 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(1):181.PubMedPubMedCentralCrossRef
Metadata
Title
The epidemiology and detectability of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in low, moderate and high transmission settings in Ethiopia
Authors
Elifaged Hailemeskel
Surafel K Tebeje
Sinknesh W. Behaksra
Girma Shumie
Getasew Shitaye
Migbaru Keffale
Wakweya Chali
Abrham Gashaw
Temesgen Ashine
Chris Drakeley
Teun Bousema
Endalamaw Gadisa
Fitsum G. Tadesse
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2021
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-021-03587-4

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