Systematic Review of Sub-microscopic P. vivax Infections: Prevalence and Determining Factors

Background Sub-microscopic (SM) Plasmodium infections represent transmission reservoirs that could jeopardise malaria elimination goals. A better understanding of the epidemiology of these infections and factors contributing to their occurrence will inform effective elimination strategies. While the epidemiology of SM P. falciparum infections has been documented, that of SM P. vivax infections has not been summarised. The objective of this study is to address this deficiency. Methodology/Principal Findings A systematic search of PubMed was conducted, and results of both light microscopy (LM) and polymerase chain reaction (PCR)-based diagnostic tests for P. vivax from 44 cross-sectional surveys or screening studies of clinical malaria suspects were analysed. Analysis revealed that SM P. vivax is prevalent across different geographic areas with varying transmission intensities. On average, the prevalence of SM P. vivax in cross-sectional surveys was 10.9%, constituting 67.0% of all P. vivax infections detected by PCR. The relative proportion of SM P. vivax is significantly higher than that of the sympatric P. falciparum in these settings. A positive relationship exists between PCR and LM P. vivax prevalence, while there is a negative relationship between the proportion of SM P. vivax and the LM prevalence for P. vivax. Amongst clinical malaria suspects, however, SM P. vivax was not identified. Conclusions/Significance SM P. vivax is prevalent across different geographic areas, particularly areas with relatively low transmission intensity. Diagnostic tools with sensitivity greater than that of LM are required for detecting these infection reservoirs. In contrast, SM P. vivax is not prevalent in clinical malaria suspects, supporting the recommended use of quality LM and rapid diagnostic tests in clinical case management. These findings enable malaria control and elimination programs to estimate the prevalence and proportion of SM P. vivax infections in their settings, and develop appropriate elimination strategies to tackle SM P. vivax to interrupt transmission.

[1]  C. Gorrini,et al.  An 8-year survey on the occurrence of imported malaria in a nonendemic area by microscopy and molecular assays. , 2008, Diagnostic microbiology and infectious disease.

[2]  H. D. del Portillo,et al.  High levels of IgG3 anti ICB2-5 in Plasmodium vivax-infected individuals who did not develop symptoms , 2013, Malaria Journal.

[3]  N. Speybroeck,et al.  Assessing malaria transmission in a low endemicity area of north-western Peru , 2013, Malaria Journal.

[4]  Chris J Drakeley,et al.  Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. , 2009, The Journal of infectious diseases.

[5]  E. P. Camargo,et al.  High prevalence of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in native Amazonian populations. , 2002, The American journal of tropical medicine and hygiene.

[6]  J. Coura,et al.  Age-dependent acquisition of protective immunity to malaria in riverine populations of the Amazon Basin of Brazil. , 2009, The American journal of tropical medicine and hygiene.

[7]  K. Kain,et al.  Impact of microscopy error on estimates of protective efficacy in malaria-prevention trials. , 2002, The Journal of infectious diseases.

[8]  P. Wilairat,et al.  A highly sensitive, rapid, and simple polymerase chain reaction-based method to detect human malaria (Plasmodium falciparum and Plasmodium vivax) in blood samples. , 1994, The American journal of tropical medicine and hygiene.

[9]  Hyung-Hwan Kim,et al.  Prevalence of Plasmodium vivax VK210 and VK247 subtype in Myanmar , 2010, Malaria Journal.

[10]  J. Roberts,et al.  A retrospective examination of the effect of fever and microgametocyte count on mosquito infection on humans infected with Plasmodium vivax. , 2004, The American journal of tropical medicine and hygiene.

[11]  R. Haque,et al.  High prevalence of asymptomatic malaria in south-eastern Bangladesh , 2014, Malaria Journal.

[12]  M. Nowak,et al.  Periodic and chaotic host-parasite interactions in human malaria. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[13]  C. King,et al.  Age-acquired immunity to a Plasmodium vivax invasion ligand, the duffy binding protein. , 2002, The Journal of infectious diseases.

[14]  Shweta Sharma,et al.  Field and laboratory comparative evaluation of rapid malaria diagnostic tests versus traditional and molecular techniques in India , 2010, Malaria Journal.

[15]  R. Sauerwein,et al.  Submicroscopic Plasmodium falciparum gametocyte densities frequently result in mosquito infection. , 2007, The American journal of tropical medicine and hygiene.

[16]  A. Saul,et al.  Diagnosis of malaria in a remote area of the Philippines: comparison of techniques and their acceptance by health workers and the community. , 2001, Bulletin of the World Health Organization.

[17]  Organización Mundial de la Salud.  Guidelines for the treatment of malaria , 2010 .

[18]  P. Siba,et al.  Differential Patterns of Infection and Disease with P. falciparum and P. vivax in Young Papua New Guinean Children , 2010, PloS one.

[19]  J. T. Williams,et al.  Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum. , 2000, Molecular biology and evolution.

[20]  Kanyanan Kritsiriwuthinan,et al.  Molecular screening of Plasmodium infections among migrant workers in Thailand. , 2011, Journal of vector borne diseases.

[21]  M. Alpers,et al.  Random distribution of mixed species malaria infections in Papua New Guinea. , 2000, The American journal of tropical medicine and hygiene.

[22]  S. Malik,et al.  Prevalence and distribution of human Plasmodium infection in Pakistan , 2013, Malaria Journal.

[23]  S. P. Kachur,et al.  Prevalence of malaria parasitemia and accuracy of microscopic diagnosis in Haiti, October 1995. , 1998, Revista panamericana de salud publica = Pan American journal of public health.

[24]  Thomas A. Smith,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 , 2009, Malaria Journal.

[25]  O. Branch,et al.  Plasmodium falciparum Genetic Diversity Maintained and Amplified Over 5 Years of a Low Transmission Endemic in the Peruvian Amazon , 2010, Molecular biology and evolution.

[26]  J. Kazura,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. , 2006, The American journal of tropical medicine and hygiene.

[27]  C. Rogier,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 , 2010, Malaria Journal.

[28]  J. Daduang,et al.  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. , 2008, Parasitology international.

[29]  J. Guerreiro,et al.  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. , 2012, Genetics and molecular research : GMR.

[30]  E. Sartono,et al.  Epidemiology of Plasmodium infections in Flores Island, Indonesia using real-time PCR , 2013, Malaria Journal.

[31]  G. Snounou,et al.  Detection of malaria in Malaysia by nested polymerase chain reaction amplification of dried blood spots on filter papers. , 1996, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[32]  S. P. Kachur,et al.  Mass drug administration for malaria , 2013, The Cochrane database of systematic reviews.

[33]  J. Sattabongkot,et al.  Infectivity of Asymptomatic Plasmodium-Infected Human Populations to Anopheles dirus Mosquitoes in Western Thailand , 2004, Journal of medical entomology.

[34]  R. Gilman,et al.  Endemic malaria in the Peruvian Amazon region of Iquitos. , 2003, The American journal of tropical medicine and hygiene.

[35]  A. Tami,et al.  ama1 Genes of Sympatric Plasmodium vivax and P. falciparum from Venezuela Differ Significantly in Genetic Diversity and Recombination Frequency , 2008, PloS one.

[36]  A. Falqueto,et al.  Epidemiologic aspects of the malaria transmission cycle in an area of very low incidence in Brazil , 2007, Malaria journal.

[37]  C. Putaporntip,et al.  Simultaneous detection of Plasmodium vivax and Plasmodium falciparum gametocytes in clinical isolates by multiplex-nested RT-PCR , 2012, Malaria Journal.

[38]  C. Wongsrichanalai,et al.  Dependence of malaria detection and species diagnosis by microscopy on parasite density. , 2003, The American journal of tropical medicine and hygiene.

[39]  P. Chiodini,et al.  Accuracy of routine laboratory diagnosis of malaria in the United Kingdom. , 1994, Journal of clinical pathology.

[40]  J. Sattabongkot,et al.  Comparison of artificial membrane feeding with direct skin feeding to estimate the infectiousness of Plasmodium vivax gametocyte carriers to mosquitoes. , 2003, The American journal of tropical medicine and hygiene.

[41]  Prevalence of imported malaria in Parma during 2005-2006. , 2007, Acta bio-medica : Atenei Parmensis.

[42]  T. Theander,et al.  Detection of very low level Plasmodium falciparum infections using the nested polymerase chain reaction and a reassessment of the epidemiology of unstable malaria in Sudan. , 1996, The American journal of tropical medicine and hygiene.

[43]  Aldina Barral,et al.  Towards a precise test for malaria diagnosis in the Brazilian Amazon: comparison among field microscopy, a rapid diagnostic test, nested PCR, and a computational expert system based on artificial neural networks , 2010, Malaria Journal.

[44]  David L. Smith,et al.  Geographical variation in Plasmodium vivax relapse , 2014, Malaria Journal.

[45]  O. Fernandes,et al.  Cross sectional study reveals a high percentage of asymptomatic Plasmodium vivax infection in the Amazon Rio Negro area, Brazil. , 2007, Revista do Instituto de Medicina Tropical de Sao Paulo.

[46]  M. De Donato,et al.  Comparison of the diagnosis of malaria by microscopy, immunochromatography and PCR in endemic areas of Venezuela. , 2007, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[47]  C. Rogier,et al.  Towards high-throughput molecular detection of Plasmodium: new approaches and molecular markers , 2009, Malaria Journal.

[48]  T. Smith,et al.  The impact of indoor residual spraying with malathion on malaria in refugee camps in eastern Sudan. , 2001, Acta tropica.

[49]  S. Briolant,et al.  Malaria prevalence and morbidity among children reporting at health facilities in Nouakchott, Mauritania. , 2011, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[50]  Q. Cheng,et al.  Population genetics of Plasmodium falciparum and Plasmodium vivax and asymptomatic malaria in Temotu Province, Solomon Islands , 2013, Malaria Journal.

[51]  J. M. Rubio,et al.  Usefulness of Seminested Multiplex PCR in Surveillance of Imported Malaria in Spain , 1999, Journal of Clinical Microbiology.

[52]  W. Hawley,et al.  The baseline distribution of malaria in the initial phase of elimination in Sabang Municipality, Aceh Province, Indonesia , 2012, Malaria Journal.

[53]  J. Trape,et al.  Preliminary study of malaria incidence in Nouakchott, Mauritania , 2009, Malaria Journal.

[54]  Teun Bousema,et al.  Factors determining the occurrence of submicroscopic malaria infections and their relevance for control , 2012, Nature Communications.

[55]  D. Durrheim,et al.  Diagnostic disagreement--the lessons learnt from malaria diagnosis in Mpumalanga. , 1997, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[56]  M. Gatton,et al.  A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting , 2010, Malaria Journal.

[57]  M. Tada,et al.  The Dynamics of Transmission and Spatial Distribution of Malaria in Riverside Areas of Porto Velho, Rondônia, in the Amazon Region of Brazil , 2010, PloS one.

[58]  K. Thimasarn,et al.  Comparison of field and expert laboratory microscopy for active surveillance for asymptomatic Plasmodium falciparum and Plasmodium vivax in western Thailand. , 2002, The American journal of tropical medicine and hygiene.

[59]  R. Hallett,et al.  Various pfcrt and pfmdr1 Genotypes of Plasmodium falciparum Cocirculate with P. malariae, P. ovale spp., and P. vivax in Northern Angola , 2012, Antimicrobial Agents and Chemotherapy.

[60]  D. Kwiatkowski,et al.  An analysis of the temperature effects of fever on the intra-host population dynamics of Plasmodium falciparum , 1998, Parasitology.