Review
The essential role of infection-detection technologies for malaria elimination and eradication

https://doi.org/10.1016/j.pt.2014.03.003Get rights and content

Highlights

  • Malaria elimination goals require active infection detection.

  • The epidemiology of low prevalence regions drives active infection tactics.

  • New diagnostic tools can improve efficiencies for malaria elimination programs.

  • New diagnostics should be guided by thoughtful target product profile development.

Recent emphasis on malaria elimination and eradication (E&E) goals is changing the way that experts evaluate malaria diagnostic tools and tactics. As prevalence declines, the focus of malaria management is pivoting toward low-density, subclinical infections and geographically and demographically concentrated reservoirs. These and other changes present challenges and opportunities for innovations in malaria diagnostics aimed at meeting the needs of malaria elimination programs. Developing such technologies requires a review of the operational approaches to detecting malaria infections in areas of declining prevalence. Here we review recent research on epidemiology and biology related to malaria elimination and operational factors that influence E&E strategies. We further propose use-scenarios and a target product profile framework to define and prioritize the required attributes of infection-detection technologies.

Section snippets

Malaria diagnostic priorities

Malaria control efforts have yielded substantial progress toward reducing the burden of malaria. In the past decade, cases of malaria fell by an estimated 274 million and malaria-related deaths were reduced by 1.1 million compared with the previous decade [1]. However, the emergence of multiple forms of resistance, the cost of sustained control efforts, and the long history of malaria resurgence [2] following near elimination have fueled recent policies, guidance [3], and funding dedicated to

Elimination and eradication goals

The WHO has established a clear distinction between the programmatic goals of malaria control, elimination, and eradication [9]. Although the goal of malaria control is to reduce morbidity and mortality, the goal of malaria elimination is to reduce malaria transmission to zero in a given geographic region. Sustained elimination in all regions over an extended period of time is a prerequisite for malaria eradication, defined as the permanent reduction to zero of the worldwide incidence [1].

The dynamic epidemiology of elimination

Malaria has often been described as heterogeneous to address wide variations in phenotype, vector–host reactions, and spatial distribution of disease [14]. Despite this variability, some general themes about the epidemiology of low-prevalence malaria can be inferred: (i) there is an increased contribution to transmission from subclinical individuals and from infections that are undetectable by microscopy and RDTs; (ii) defined parasite reservoirs, a bellwether of elimination, represent both

Distinguishing use-scenarios

In light of the dynamic epidemiology of malaria elimination and the tactics under development to most efficiently identify and treat infection, use-scenarios present a useful, outcome-oriented framework for classifying and distinguishing ID methods. A thorough understanding of each use-scenario, including identifying the probable location, user, training, infrastructure, and other constraints, is essential to subsequently assigning attribute requirements for hypothetical tools that provide the

Target product profiles

A TPP [77] is a strategic planning tool that is used to facilitate communication among all product-development stakeholders. TPPs drive product-development thinking by beginning with the end goal in mind [78]. This review of the use-scenarios categorized in Figure 1 suggests that various technical improvements can be made to existing malaria ID technologies to adapt them to E&E tactics. Yet the distinct use-scenarios described in Figure 1 each correspond to a unique set of performance and user

Concluding remarks and future perspectives

The ability to accurately detect malaria infection in all individuals and in all populations is fundamental to achieving E&E goals. However, the detection of low-level infections is notoriously inaccurate with currently available RDTs and microscopy, and PCR is expensive and infeasible for field use [5]. This suggests that new diagnostic tools are needed with user requirements and performance attributes that are appropriate for application within the continuum of malaria elimination

Glossary

Active infection detection (active ID)
the detection of malaria (clinical and subclinical) infections at community and household levels in population groups that are considered to be high risk.
Border testing
a proactive ID tactic aimed at preventing cross-border transmission at checkpoints. Border testing may be preceded by fever screening followed by testing of all patients with a recent history of malaria symptoms.
Community testing
a reactive ID tactic to identify and treat infected persons

References (78)

  • J.M. Cohen

    Malaria resurgence: a systematic review and assessment of its causes

    Malar. J.

    (2012)
  • WHO

    Malaria Elimination: A Field Manual for Low and Moderate Endemic Countries

    (2007)
  • Foundation for Innovative New Diagnostics

    Malaria Rapid Diagnostic Test Performance: Results of WHO Product Testing of Malaria RDTs: Round 4 (2012)

    (2012)
  • A research agenda for malaria eradication: diagnoses and diagnostics

    PLoS Med.

    (2011)
  • D.D. Laishram

    The complexities of malaria disease manifestations with a focus on asymptomatic malaria

    Malar. J.

    (2012)
  • WHO

    Global Malaria Control and Elimination: Report of a Technical Review

    (2008)
  • J.M. Cohen

    How absolute is zero? An evaluation of historical and current definitions of malaria elimination

    Malar. J.

    (2010)
  • E. Pampana

    A Textbook of Malaria Eradication

    (1963)
  • C.C. Campbell et al.

    Malaria in Africa can be eliminated

    Am. J. Trop. Med. Hyg.

    (2011)
  • C. Chiyaka

    Infectious disease. The stability of malaria elimination

    Science

    (2013)
  • K. Mendis

    From malaria control to eradication: the WHO perspective

    Trop. Med. Int. Health

    (2009)
  • J. Bousema

    Plasmodium falciparum gametocyte carriage in asymptomatic children in western Kenya

    Malar. J.

    (2004)
  • I. Harris

    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

    Malar. J.

    (2010)
  • L.C. Okell

    Factors determining the occurrence of submicroscopic malaria infections and their relevance for control

    Nat. Commun.

    (2012)
  • M.D. Young et al.

    The infectivity of native malarias in South Carolina to Anopheles quadrimaculatus

    Am. J. Trop. Med. Hyg.

    (1948)
  • F.P. Alves

    Asymptomatic carriers of Plasmodium spp. as infection source for malaria vector mosquitoes in the Brazilian Amazon

    J. Med. Entomol.

    (2005)
  • G.M. Jeffrey et al.

    Infectivity to mosquitoes of Plasmodium falciparum as related to gametocyte density and duration of infection

    Am. J. Trop. Med. Hyg.

    (1955)
  • V. Delley

    What does a single determination of malaria parasite density mean? A longitudinal survey in Mali

    Trop. Med. Int. Health

    (2000)
  • W.P. O’Meara

    Sources of variability in determining malaria parasite density by microscopy

    Am. J. Trop. Med. Hyg.

    (2005)
  • A. Farnert

    Daily dynamics of Plasmodium falciparum subpopulations in asymptomatic children in a holoendemic area

    Am. J. Trop. Med. Hyg.

    (1997)
  • P. Van den Eede

    Plasmodium vivax sub-patent infections after radical treatment are common in Peruvian patients: results of a 1-year prospective cohort study

    PLoS ONE

    (2011)
  • S. Incardona

    Large-scale malaria survey in Cambodia: novel insights on species distribution and risk factors

    Malar. J.

    (2007)
  • M. Littrell

    Case investigation and reactive case detection for malaria elimination in northern Senegal

    Malar. J.

    (2013)
  • T. Bousema

    Hitting hotspots: spatial targeting of malaria for control and elimination

    PLoS Med.

    (2012)
  • P. Bejon

    Stable and unstable malaria hotspots in longitudinal cohort studies in Kenya

    PLoS Med.

    (2010)
  • C. Roper

    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

    Am. J. Trop. Med. Hyg.

    (1996)
  • J.Y. Kim

    Comparison of rapid diagnostic tests for the detection of Plasmodium vivax malaria in South Korea

    PLoS ONE

    (2013)
  • Ministry of Health (MOH)/Solomon Islands Vector Borne Disease Control Program

    Malaria Information System Database Query

    (2012)
  • J. Manuel Ramos

    Change in epidemiology of malaria infections in a rural area in Ethiopia

    J. Travel Med.

    (2005)
  • Cited by (38)

    • A focus on improving molecular diagnostic approaches to malaria control and elimination in low transmission settings: Review

      2019, Parasite Epidemiology and Control
      Citation Excerpt :

      Elimination is attaining malaria transmission at zero level in each geographic region and elimination in all regions leads to malaria eradication which is the permanent reduction to zero incidence globally (World Health Organization, 2018a). The context of malaria elimination goals paves a way for changing diagnostic tools and since the prevalence of malaria is declining, its management is focused on subclinical infections and on geographically as well as demographically concentrated human reservoirs (Tietje et al., 2014). There is no universal definition for asymptomatic parasitemias but most of the definitions involve detection of sexual or asexual parasites in the absence of symptom of malaria (mostly fever) and it excludes the dormant liver stage (Lindblade et al., 2013).

    • Asymptomatic plasmodial infection in Colombian pregnant women

      2017, Acta Tropica
      Citation Excerpt :

      Asymptomatic plasmodial infection (API) has been recognized since many decades ago, but only now, it is receiving attention because of the current antimalarial program goals (control, elimination, eradication) (Tietje et al., 2014).

    • New molecular detection methods of malaria parasites with multiple genes from genomes

      2016, Acta Tropica
      Citation Excerpt :

      Hence it is very important to have a rapid, sensitive and specific method for the detection of malaria parasites in febrile patients as well as in asymptomatic individuals. Precise identification of malaria disease may play a key role in planning, targeting and evaluating malaria control efforts in low, medium and high malaria endemic areas (Alonso et al., 2011; Tietje et al., 2014; Sturrock et al., 2013). We have developed methods using the real-time PCR based assays for the diagnosis of malaria caused by Pf and Pv, which have shown good threshold sensitivity value in the blood samples even with low parasitemia (Figs. 3 and 4).

    • Impact of Malaria in Pregnancy as Latin America Approaches Elimination

      2016, Trends in Parasitology
      Citation Excerpt :

      For the context of Latin America, it will be important to include species identification with any diagnostic test for malaria in order to guide treatment. Pregnant women are among the more accessible populations for active case detection and can be considered one of the so-called ‘hot pops’ (target populations) for interventions directed toward elimination [76]. Support for women to attend antenatal clinics ensures better care, and in turn can provide opportunities for screening women during pregnancy by sensitive methods to identify asymptomatic sub-microscopic infections.

    View all citing articles on Scopus
    View full text