Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Malaria Journal
Published in: Malaria Journal 1/2015

Open Access 01-12-2015 | Research

A systematic review of sub-microscopic Plasmodium vivax infection

Authors: Clarissa M. Moreira, Mahmoud Abo-Shehada, Ric N. Price, Chris J. Drakeley

Published in: Malaria Journal | Issue 1/2015

Login to get access

Abstract

Background

An accurate estimate of Plasmodium vivax prevalence is essential for the successful implementation of malaria control and elimination programmes. Prevalence estimates both inform control strategies and are used in their evaluation. Light microscopy is the main method for detecting Plasmodium parasitaemia in the peripheral blood, but compared to molecular diagnostics, such as polymerase chain reaction (PCR), has limited sensitivity.

Methods

A systematic review and meta-analysis was conducted to assess the effect of detection method on the prevalence of P. vivax and to quantify the extent to which P. vivax infections are undetected by microscopy. Embase, Medline and the Cochrane Database were searched for studies reporting prevalence by PCR and by microscopy and that contained all of the following key words: vivax, PCR, and malaria. Prevalence estimates and study meta-data were extracted systematically from each publication. Combined microscopy:PCR prevalence ratios were estimated by random effects meta-analysis. Sensitivity and specificity of microscopy were calculated using PCR as the gold standard.

Results

Of 874 studies reviewed, 40 met the criteria for inclusion contributing 54 prevalence pairs. The prevalence of P. vivax infection measured by PCR was consistently higher than the prevalence measured by microscopy with sub-patent parasitaemia. The mean prevalence of infection detected by microscopy was 67 % (95 % CI 59–73 %) lower than the prevalence detected by PCR. The detection of sub-patent parasitaemia did not vary according to the microscopy method (thick or, thick and thin smears), the PCR prevalence (as a measure of the true P. vivax prevalence), the type of blood used or DNA extraction method.

Conclusions

Quantifying P. vivax parasitaemia by PCR rather than microscopy consistently increased prevalence estimates by a factor of 2.3. Whilst the sensitivity of microscopy can be improved by better methods, molecular methods have potential to be scaled up to improve the detection of P. vivax transmission reservoirs.
Appendix
Available only for authorised users
Literature
1.
Guerra CA, Howes RE, Patil AP, Gething PW, Van Boeckel TP, Temperley WH, et al. The international limits and population at risk of Plasmodium vivax transmission in 2009. PLoS Negl Trop Dis. 2010;4:11.CrossRef
2.
Barcus MJ, Basri H, Picarima H, Manyakori C, Sekartuti, Elyazar I, et al. Demographic risk factors for severe and fatal vivax and falciparum malaria among hospital admissions in northeastern Indonesian Papua. Am J Trop Med Hyg. 2007;77:984–91.PubMed
3.
Looareesuwan S, White N, Chittamas S, Bunnag D, Harinasuta T. High rate of Plasmodium vivax following treatment of falciparum malaria in Thailand. Lancet. 1987;7:1052–5.CrossRef
4.
5.
WHO. World malaria report 2008. Geneva: World Health Organization; 2008.
6.
WHO. Guidelines for the diagnosis and treatment of malaria in the African region 2003. Geneva: World Health Organization; 2003.
7.
Coura JR, Suárez-Mutis M, Ladeia-Andrade S. A new challenge for malaria control in Brazil: asymptomatic Plasmodium infection—a review. Mem Inst Oswaldo Cruz. 2006;101:229–37.PubMed
8.
Roshanravan B, Kari E, Gilman RH, Cabrera L, Lee E, Metcalfe J, et al. Endemic malaria in the Peruvian Amazon region of Iquitos. Am J Trop Med Hyg. 2003;69:45–52.PubMed
9.
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.
10.
Carter R, Mendis KN. Evolutionary and historical aspects of the burden of malaria. Clinic. 2002;15:564–94.
11.
Bousema T, Dinglasan RR, Morlais I, Gouagna LC, van Warmerdam T, Awono-Ambene PH, et al. Mosquito feeding assays to determine the infectiousness of naturally infected Plasmodium falciparum gametocyte carriers. PLoS One. 2012;7:e42821.PubMedCentralCrossRefPubMed
12.
Pourmoshtagh H, Fahimzah A, Karimi A. Comparison of polymerase chain reaction (PCR) and peripheral blood smear (PBS) for diagnosis of asymptomatic malaria parasitemia. Iran J Clin Infect Dis. 2012;7:7–9.
13.
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
14.
Cheng Q, Cunningham J, Gatton ML. Systematic review of sub-microscopic P. vivax infections: prevalence and determining factors. PLoS Negl Trop Dis. 2015;9:e3413.PubMedCentralCrossRefPubMed
15.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.PubMedCentralCrossRefPubMed
16.
Harris RJ, Bradburn MJ, Deeks JJ, Hardbord RM, Altman DG, Sterne J. Metan: fixed- and random-effects meta-analysis. Stata J. 2008;8:3–28.
17.
Alves FP, Durlacher RR, Menezes MJ, Krieger H, Silva LHP, Camargo EP. High prevalence of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in native Amazonian populations. Am J Trop Med Hyg. 2002;66:641–8.PubMed
18.
Asih PB, Rozi IE, Herdiana Pratama NR, Hidayati AP, Marantina SS, et al. The baseline distribution of malaria in the initial phase of elimination in Sabang Municipality, Aceh Province, Indonesia. Malar J. 2012;11:291.PubMedCentralCrossRefPubMed
19.
Barbosa S, Gozze AB, Lima NF, Batista CL, Bastos MDS, Nicolete VC, et al. Epidemiology of disappearing Plasmodium vivax malaria: a case study in rural Amazonia. PLoS Negl Trop Dis. 2014;8:e3109.PubMedCentralCrossRefPubMed
20.
Cerutti C, Boulos M, Coutinho AF, Hatab MD, Falqueto A, Rezende HR, et al. Epidemiologic aspects of the malaria transmission cycle in an area of very low incidence in Brazil. Malar J. 2007;6:33.CrossRefPubMed
21.
Coleman RE, Sattabongkot J, Promstaporm S, Maneechai N, Tippayachai B, Kengluecha A, et al. Comparison of PCR and microscopy for the detection of asymptomatic malaria in a Plasmodium falciparum/vivax endemic area in Thailand. Malar J. 2006;5:121.PubMedCentralCrossRefPubMed
22.
Cole-tobian JL, Corte A, Baisor M, Kastens W, Xainli J, Bockarie M, et al. Age-acquired immunity to a Plasmodium vivax invasion ligand, the Duffy binding protein. J Infect Dis. 2002;186:531–9.CrossRefPubMed
23.
Congpuong K, Saejeng A, Sug-Aram R, Aruncharus S, Darakapong A, Meshnick SR, et al. Mass blood survey for malaria: pooling and real-time PCR combined with expert microscopy in north-west Thailand. Malar J. 2012;11:288.PubMedCentralCrossRefPubMed
24.
Da Silva NS, da Silva-Nunes M, Malafronte RS, Menezes MJ, D’Arcadia RR, Komatsu NT, et al. Epidemiology and control of frontier malaria in Brazil: lessons from community-based studies in rural Amazonia. Trans R Soc Trop Med Hyg. 2010;104:343–50.CrossRefPubMed
25.
Fançony C, Gamboa D, Sebastião Y, Hallett R, Sutherland C, Sousa-Figueiredo JC, et al. Various pfcrt and pfmdr1 genotypes of Plasmodium falciparum cocirculate with P. malariae, P. ovale spp., and P. vivax in northern Angola. Antimicrob Agents Chemother. 2012;56:5271–7.PubMedCentralCrossRefPubMed
26.
Gunasekera AW, Abeyasinghe RR, Premawansa S, Fernando SD. Usefulness of polymerase chain reaction to supplement field microscopy in a pre-selected population with a high probability of malaria infections. Am J Trop Med Hyg. 2011;85:6–11.PubMedCentralCrossRef
27.
Kaisar MM, Supali T, Wiria AE, Hamid F, Wammes LJ, Sartono E, et al. Epidemiology of Plasmodium infections in Flores Island, Indonesia using real-time PCR. Malar J. 2013;12:169.PubMedCentralCrossRefPubMed
28.
Kaneko A, Chaves LF, Taleo G, Kalkoa M, Isozumi R, Wickremasinghe R, et al. Characteristic age distribution of Plasmodium vivax infections after malaria elimination on Aneityum Island, Vanuatu. Infect Immun. 2014;82:243–52.PubMedCentralCrossRefPubMed
29.
Kano FS, Sanchez BA, Sousa TN, Tang ML, Saliba J, Oliveira FM, et al. Plasmodium vivax Duffy binding protein: baseline antibody responses and parasite polymorphisms in a well-consolidated settlement of the Amazon Region. Trop Med Int Health. 2012;17:989–1000.CrossRefPubMed
30.
Kasehagen LJ, Mueller I, McNamara DT, Bockarie MJ, Rare L, Lorry K, et al. Changing patterns of Plasmodium blood-stage infections in the Wosera region of Papua New Guinea monitored by light microscopy and high throughput PCR diganosis. Am J Trop Med Hyg. 2013;75:588–96.
31.
Katsuragawa TH, Gil LH, Tada MS, de Almeida e Silva A, Costa JD, Araújo Mda S, et al. The dynamics of transmission and spatial distribution of malaria in riverside areas of Porto Velho, Rondônia, in the Amazon region of Brazil. PLoS one. 2010;5:e9245.PubMedCentralCrossRefPubMed
32.
Khaminsou N, Kritpetcharat O, Daduang J, Kritpetcharat P. A survey of malarial infection in endemic areas of Savannakhet province, Lao PDR and comparative diagnostic efficiencies of Giemsa staining, acridine orange staining, and semi-nested multiplex PCR. Parasitol Int. 2008;57:143–9.CrossRefPubMed
33.
Ladeia-Andrade S, Ferreira MU, de Carvalho ME, Curado I, Coura JR. Age-dependent acquisition of protective immunity to malaria in riverine populations of the Amazon Basin of Brazil. Am J Trop Med Hyg. 2009;80:452–9.PubMed
34.
Li P, Zhao Z, Wang Y, Xing H, Parker DM, Yang Z, et al. Nested PCR detection of malaria directly using blood filter paper samples from epidemiological surveys. Malar J. 2014;13:175.PubMedCentralCrossRefPubMed
35.
Lin E, Kiniboro B, Gray L, Dobbie S, Robinson L, Stanisic D, et al. Differential patterns of infection and disease with P. falciparum and P. vivax in young Papua New Guinean children. PLoS One. 2010;5:e9047.PubMedCentralCrossRefPubMed
36.
Mehlotra RK, Kasehagen LJ, Baisor M, Lorry K, Kazura JW, Bockarie MJ, et al. Malaria infections are randomly distributed in diverse holoendemic areas of Papua New Guinea. Am J Trop Med Hyg. 2002;67:555–62.PubMedCentralPubMed
37.
Mehlotra RK, Lorry K, Kastens W, Miller SM, Alpers MP, Bockarie M, et al. Random distribution of mixed species malaria infections in Papua New Guinea. Am J Trop Med Hyg. 2000;62:225–31.PubMed
38.
Mueller I, Widmer S, Michel D, Maraga S, McNamara DT, Kiniboro B, et al. High sensitivity detection of Plasmodium species reveals positive correlations between infections of different species, shifts in age distribution and reduced local variation in Papua New Guinea. Malar J. 2009;8:41.PubMedCentralCrossRefPubMed
39.
Van Nguyen H, van den Eede P, van Overmeir C, Thang ND, Hung LX, D’Alessandro U, et al. Marked age-dependent prevalence of symptomatic and patent infections and complexity of distribution of human Plasmodium species in central Vietnam. Am J Trop Med Hyg. 2012;87:989–95.PubMedCentralCrossRefPubMed
40.
Patel JC, Lucchi NW, Srivastava P, Lin JT, Sug-Aram R, Aruncharus S, et al. Field evaluation of a real-time fluorescence loop-mediated isothermal amplification assay, RealAmp, for the diagnosis of malaria in Thailand and India. J Infect Dis. 2014;210:1180–7.CrossRefPubMed
41.
Rodulfo H, De Donato M, Mora R, Gonzalez L, Contreras CE. Comparison of the diagnosis of malaria by microscopy, immunochromatography and PCR in endemic areas of Venezuela. Braz J Med Biomed Res. 2007;40:535–43.
42.
Rogawski ET, Congpuong K, Sudathip P, Satimai W, Sug-aram R, Aruncharus S, et al. Active case detection with pooled real-time PCR to eliminate malaria in Trat province, Thailand. Am J Trop Med Hyg. 2012;86:789–91.PubMedCentralCrossRefPubMed
43.
Rosanas-Urgell A, Mueller D, Betuela I, Barnadas C, Iga J, Zimmerman P, et al. Comparison of diagnostic methods for the detection and quantification of the four sympatric Plasmodium species in field samples from Papua New Guinea. Malar J. 2010;9:361.PubMedCentralCrossRefPubMed
44.
Rosas-Aguirre A, Llanos-Cuentas A, Speybroeck N, Cook J, Contreras-Mancilla J, Soto V, et al. Assessing malaria transmission in a low endemicity area of north-western Peru. Malar J. 2013;12:339.PubMedCentralCrossRefPubMed
45.
Rubio JM, Benito A, Roche J, Berzosa PJ, García ML, Micó M, et al. Semi-nested, multiplex polymerase chain reaction for detection of human malaria parasites and evidence of Plasmodium vivax infection in Equatorial Guinea. Am J Trop Med Hyg. 1999;60:183–7.PubMed
46.
Scopel KKG, Fontes CJF, Nunes ÁC, Horta MF, Braga ÉM. High prevalence of Plamodium malariae infections in a Brazilian Amazon endemic area (Apiacás—Mato Grosso State) as detected by polymerase chain reaction. Acta Trop. 2004;90:61–4.CrossRefPubMed
47.
Singh B, Cox-Singh J, Miller AO, Abdullah MS, Snounou G. Detection of malaria in Malaysia by nested polymerase amplification of dried blood spots on filter papers chain reaction. Trans R Soc Trop Med Hyg. 1996;90:519–21.CrossRefPubMed
48.
Souza CRT, Carvalho T, Amaral RCG, Cunha LS, Cunha MG, Guerreiro JF. Prevalence of Plasmodium falciparum and P. vivax in an area of transmission located in Pará State, Brazil, determined by amplification of mtDNA using a real-time PCR assay. Genet Mol Res. 2012;11:3409–13.CrossRefPubMed
49.
Starzengruber P, Fuehrer H, Ley B, Thriemer K, Swoboda P, Habler VE, et al. High prevalence of asymptomatic malaria in South-Eastern Bangladesh. Malar J. 2014;13:1–10.CrossRef
50.
Steenkeste N, Incardona S, Chy S, Duval L, Ekala M-T, Lim P, et al. Towards high-throughput molecular detection of Plasmodium: new approaches and molecular markers. Malar J. 2009;8:86.PubMedCentralCrossRefPubMed
51.
Suárez-mutis MC, Cuervo P, Leoratti FMS, Moraes-avila SL, Ferreira AW. Plasmodium vivax infection in the Amazon Rio Negro Area, Brazil. Rev Inst Med Trop Sao Paulo. 2007;49:159–64.CrossRefPubMed
52.
Versiani FG, Almeida MEM, Melo GC, Versiani FOL, Orlandi PP, Mariúba LAM, et al. High levels of IgG3 anti ICB2-5 in Plasmodium vivax-infected individuals who did not develop symptoms. Malar J. 2013;12:294.PubMedCentralCrossRefPubMed
53.
Vo TKD, Bigot P, Gazin P, Sinou V, De Pina JJ, Huynh DC, et al. Evaluation of a real-time PCR assay for malaria diagnosis in patients from Vietnam and in returned travellers. Trans R Soc Trop Med Hyg. 2007;101:422–8.CrossRefPubMed
54.
Wang B, Han S-S, Cho C, Han J-H, Cheng Y, Lee S-K, et al. Comparison of microscopy, nested-PCR, and real-time-PCR assays using high-throughput screening of pooled samples for diagnosis of malaria in asymptomatic carriers from areas of endemicity in Myanmar. J Clin Microbiol. 2014;52:1838–45.PubMedCentralCrossRefPubMed
55.
De Almeida A, Rosário VE, Henriques G, Arez AP, Cravo P. Plasmodium vivax in the Democratic Republic of East Timor: parasite prevalence and antifolate resistance-associated mutations. Acta Trop. 2010;115:288–92.CrossRefPubMed
56.
Gomes ADC, Paula MB De, Duarte AMRDC, Lima MA, Malafronte RDS, Mucci LF, Gotlieb SLD, Natal D. Epidemiological and ecological aspects related to malaria in the area of influence of the lake at Porto Primavera dam, in western São Paulo State, Brazil. Rev Inst Med Trop Sao Paulo. 2008;50:287–95.CrossRef
57.
Das MK, Joshi H, Verma A, Singh SS, Adak T. Malaria among the Jarawas, a primitive and isolated tribe on the Andaman islands, India. Ann Trop Med Parasitol. 2005;99:545–52.CrossRefPubMed
58.
Turki H, Zoghi S, Mehrizi AA, Zakeri S, Raeisi A, Khazan H, Haghdoost A. Absence of asymptomatic malaria infection in endemic area of bashagard district, hormozgan province, iran. Iran J Parasitol. 2012;7:36–44.PubMedCentralPubMed
59.
Zoghi S, Mehrizi AA, Raeisi A, Haghdoost AA, Turki H, Safari R, Kahanali AA, Zakeri S. Survey for asymptomatic malaria cases in low transmission settings of Iran under elimination programme. Malar J. 2012;11:126.PubMedCentralCrossRefPubMed
60.
WHO. Basic malaria microscopy part 1: learner's guide 1991. Geneva: World Health Organization; 1991.
61.
Kasehagen LJ, Mueller I, McNamara DT, Bockarie MJ, Kiniboro B, Rare L, et al. Changing patterns of Plasmodium blood-stage infections in the Wosera region of Papua New Guinea monitored by light microscopy and high throughput PCR diagnosis. Am J Trop Med Hyg. 2006;75:588–96.PubMedCentralPubMed
62.
Mcnamara DT, Cole-Tobian J. Diagnosing infection levels of four human malaria parasite species by a polymerase chain reaction/microsphere-based assay. Am J Trop Med Hyg. 2013;74:413–21.
63.
Taylor S, Juliano J, Trottman P, Griffin J, Landis S, Kitsa P, et al. High-throughput pooling and real-time PCR-based strategy for malaria detection. J Clin Microbiol. 2010;48:512–9.PubMedCentralCrossRefPubMed
64.
Snounou G, Viriyakosol S, Jarra W, Thaithong S, Brown K. Identification of the four human malaria parasite species in field samples by the polymerase chain reaction and detection of a high prevalence of mixed infections. Mol Biochem Parasitol. 1993;58:283–92.CrossRefPubMed
65.
Mbakilwa H, Manga C, Kibona S, Mtei F, Meta J, Shoo A, et al. Quality of malaria microscopy in 12 district hospital laboratories in Tanzania. Pathog Glob Health. 2012;106:330–4.PubMedCentralCrossRefPubMed
66.
Meneghini R, Packer AL. Is there science beyond English? EMBO Rep. 2007;8:2–6.CrossRef
67.
68.
Lu Y, Dendukuri N, Schiller I, Joseph L. A Bayesian approach to simultaneously adjusting for verification and reference standard bias in diagnostic test studies. Stat Med. 2010;29:2532–43.CrossRefPubMed
69.
Alves FP, Gil L, Marrelli MT, Ribolla PE, Camargo EP, Da Silva LH. Asymptomatic carriers of Plasmodium spp. as infection source for malaria vector mosquitoes in the Brazilian Amazon. J Med Entomol. 2005;42:777–9.CrossRefPubMed
Metadata
Title
A systematic review of sub-microscopic Plasmodium vivax infection
Authors
Clarissa M. Moreira
Mahmoud Abo-Shehada
Ric N. Price
Chris J. Drakeley
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/s12936-015-0884-z

Other articles of this Issue 1/2015

Malaria Journal 1/2015 Go to the issue

Research

Knockdown resistance of Anopheles sinensis in Henan province, China

Research

Malaria parasite carriage and risk determinants in a rural population: a malariometric survey in Rwanda

Research

Addition of histamine to subcutaneously injected Plasmodium berghei sporozoites increases the parasite liver load and could facilitate whole-parasite vaccination

Research

A prescription for sustaining community engagement in malaria elimination on Aneityum Island, Vanuatu: an application of Health Empowerment Theory

Research

Assessing the social vulnerability to malaria in Rwanda

Research

Development of a text-messaging intervention to improve treatment adherence and post-treatment review of children with uncomplicated malaria in western Kenya

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24 to hear Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits