Malaria and the 'last' parasite: how can technology help?

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infectious disease 4 infectiousdiseases
malaria 58 infectiousdiseases
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AIDS 284 7/2018Publication date (pmc-release): 7/2018Publication date (collection): /2018AbstractMalaria, together with HIV/ AIDS , tuberculosis and hepatitis are the four most deadly infectious diseases globally. Progress in eliminating
AIDS 1398 one of the four most life-threatening infectious diseases worldwide, together with tuberculosis, HIV/ AIDS and hepatitis [[2]]. Latest data published by the World Health Organization (WHO) are staggering: more
infectious disease 342 (collection): /2018AbstractMalaria, together with HIV/AIDS, tuberculosis and hepatitis are the four most deadly infectious disease s globally. Progress in eliminating malaria has saved millions of lives, but also creates new challenges
infectious disease 1335 dates back to the 5th century BC [[1]]. Today, malaria remains one of the four most life-threatening infectious disease s worldwide, together with tuberculosis, HIV/AIDS and hepatitis [[2]]. Latest data published by the World
infectious disease 37061 within 10 min. The spatio-temporal information collected by this device can document prevalence of many infectious disease s and would allow efficient tracking of epidemics. Another approach to integrate a custom microfluidic-based
infectious disease 40053 devices coupled to phone-based readouts offer a unique opportunity to not only reduce the burden of infectious disease s, such as malaria, but also could provide tools for monitoring epidemics and elimination progress on
malaria 396 tuberculosis and hepatitis are the four most deadly infectious diseases globally. Progress in eliminating malaria has saved millions of lives, but also creates new challenges in detecting the ‘last parasite’. Effective
malaria 539 also creates new challenges in detecting the ‘last parasite’. Effective and accurate detection of malaria infections, both in symptomatic and asymptomatic individuals are needed. In this review, the current
malaria 701 individuals are needed. In this review, the current progress in developing new diagnostic tools to fight malaria is presented. An ideal rapid test for malaria elimination is envisioned with examples to demonstrate
malaria 747 progress in developing new diagnostic tools to fight malaria is presented. An ideal rapid test for malaria elimination is envisioned with examples to demonstrate how innovative technologies can assist the global
malaria 974 this disease. Diagnostic gaps where technology can bring an impact to the elimination campaign for malaria are identified. Finally, how a combination of microfluidic-based technologies and smartphone-based read-outs
malaria 1192 could potentially represent the next generation of rapid diagnostic tests is discussed.The burden of malaria The first record of malaria fevers dates back to the 5th century BC [[1]]. Today, malaria remains one
malaria 1219 the next generation of rapid diagnostic tests is discussed.The burden of malariaThe first record of malaria fevers dates back to the 5th century BC [[1]]. Today, malaria remains one of the four most life-threatening
malaria 1281 burden of malariaThe first record of malaria fevers dates back to the 5th century BC [[1]]. Today, malaria remains one of the four most life-threatening infectious diseases worldwide, together with tuberculosis,
malaria 1781 unprecedented efforts in recent years, progress has stalled. This calls for more effective tools to reduce malaria and finally to eliminate this scourge. If this historical milestone can be accomplished, it could save
malaria 2102 the ‘last’ parasiteThis review only focuses on relevant innovative diagnostic technologies for malaria elimination settings where the malaria transmission is low; therefore, there is a critical need to detect
malaria 2141 only focuses on relevant innovative diagnostic technologies for malaria elimination settings where the malaria transmission is low; therefore, there is a critical need to detect asymptomatic individuals. Together
malaria 2446 identify the invisible reservoirs. The role of innovative tools becomes crucial in the fight against malaria and the WHO identifies three strategic pillars (universal access to prevention, drugs and diagnosis,
malaria 2723 diagnostics at the point-of-care (POC) is the first step towards appropriate diagnosis and treatment for malaria infection [[5], [6]].Table 1 compares the performance of currently available malaria diagnostic tests
malaria 2809 treatment for malaria infection [[5], [6]].Table 1 compares the performance of currently available malaria diagnostic tests for case management and surveillance. The landscape for malaria diagnosis can be divided
malaria 2890 currently available malaria diagnostic tests for case management and surveillance. The landscape for malaria diagnosis can be divided into two main groups, POC methods in case management and laboratory-based methods
malaria 3452 ultra-sensitivity (less than 2 parasites/μL for both Pan and Pf-LAMP) in the field [[9], [10]], implementing malaria diagnostic tools in the field still requires addressing of several critical challenges such as simplified
malaria 3710 that require no cold chain [[11]]. Further, there is no reported literature referring to the use of malaria LAMP as a diagnostic tool in populations, or of being endorsed and procured by any programs or governments.
malaria 4147 are effective in low-resource settings (LRS) [[10], [13]–[25]].Table 1Characteristics of current malaria diagnostic tools used in case management and surveillanceLoD (p/µL or ng mL−1)Sensitivity (%) (95%
malaria 5980 availability and skills of trained microscopists, which might not always be available in the LRS, where malaria is endemic.Rapid diagnostic testsField studies have confirmed the benefits of introducing RDTs into
malaria 6249 adherence to test results, and having more rational treatments [[28], [29]]. Characteristics of current malaria RDTs are summarized in Table 2. Key advantages of RDTs are the ease to use and quick result delivery
malaria 6491 or microscopy, RDTs detect circulating antigen; therefore they can also be used to detect placental malaria [[30]]. Diagnosis of malaria in pregnancy is challenging because of placental sequestration, which is
malaria 6520 circulating antigen; therefore they can also be used to detect placental malaria [[30]]. Diagnosis of malaria in pregnancy is challenging because of placental sequestration, which is specific to Plasmodium falciparum
malaria 6748 can make microscopy detection of parasites difficult.Table 2Advantages and disadvantages of current malaria RDTsAdvantageDisadvantagesEasy to useDeletion of the Pfhrp2 gene leads to false negative RDTs (particularly
malaria 7170 stability when being stored in endemic settingsPortable and disposableInability to differentiate non-Pf malaria Require minimal laboratory infrastructure, power or external equipmentInability to distinguish current
malaria 7514 treatment efficacyAlthough using the same technology of lateral flow immunoassays, the performance of malaria RDTs varies greatly from brand-to-brand, and lot-to-lot, especially with specimens having low parasite
malaria 7804 Innovative New Diagnostics (FIND), the WHO and the Centers for Disease Control and Prevention, 293 malaria RDTs were evaluated from 2008 to 2016 [[31]]. Most of the evaluated malaria RDTs detect P. falciparum
malaria 7880 Control and Prevention, 293 malaria RDTs were evaluated from 2008 to 2016 [[31]]. Most of the evaluated malaria RDTs detect P. falciparum histidine-rich protein 2 (PfHRP2) or P. falciparum lactase dehydrogenase (PfpLDH).
malaria 9556 permission from [[36]] copyright 2014 Royal Society of Chemistry)Promising and alternative technologies for malaria detectionTable 3 summarizes six major classes of technologies used for detecting malaria and indicates
malaria 9646 technologies for malaria detectionTable 3 summarizes six major classes of technologies used for detecting malaria and indicates their maturity levels. These technologies are individually reviewed in depth elsewhere
malaria 9989 visualization of parasites [[50]–[53]]. Table 4 provides specifications of some recently entered market malaria diagnostic [[38]]. Of those market-ready products, four of them are molecular diagnostics, three are
malaria 10216 one is based on automated microscopy. Several promising proof-of-concepts for the next generation of malaria RDTs are emerging. For example, prototypes have been built to detect the presence of haemozoin in blood
malaria 11326 Homozoin-generated vapour nanobubbleTable 4Specifications of recently-entered market* technologies for malaria diagnosis.table based on information contained in Ref [[38]]TechnologyProductDeveloperDescriptionType
malaria 11728 controlMicroscopyParasightSight Diagnostics Ltd, 2014Automated microscopy suitable for processing of multiple malaria Slide readingUnder wayn/aBlood smearn/an/an/an/aMalaria RDTs**Fio-netFio Corporation, 2012Universal RDT
malaria 11888 smearn/an/an/an/aMalaria RDTs**Fio-netFio Corporation, 2012Universal RDT reader and cloud information services to improve malaria RDT quality assurance and malaria surveillanceCombination of mobile diagnostics (mobile universal reader)
malaria 11922 2012Universal RDT reader and cloud information services to improve malaria RDT quality assurance and malaria surveillanceCombination of mobile diagnostics (mobile universal reader) with cloud information servicesAutomated
malaria 12595 senstitive and specific lateral flow assay detecting novel Plasmodium proteins shed in the urine of febril malaria patientsDipstick technology (lateral flow assay)LOD 125 parasites/µL~ 20 min100 µL urinen/an/aUsable
malaria 15104 (PATH) are working on promising productsAnother example utilizes a portable breath analyzer: breaths of malaria -infected patients were found to contain terpenes, a family of aromatic chemicals that are produced by
malaria 15825 the level of terpenes detected in breath into parasite density.Specifications for a new generation of malaria RDTsDifferent settings require different target product profiles (TPP) [[8]]. Unlike previous malaria
malaria 15927 malaria RDTsDifferent settings require different target product profiles (TPP) [[8]]. Unlike previous malaria control campaigns, the key characteristics of malaria elimination efforts are to interrupt endemic transmission
malaria 15981 product profiles (TPP) [[8]]. Unlike previous malaria control campaigns, the key characteristics of malaria elimination efforts are to interrupt endemic transmission and to prevent its re-establishment [[62]].
malaria 16292 development and validation of sensitive rapid tests for mass screening in LRS. They also proposed a TPP for malaria RDTs in elimination settings, stating specific requirements for the ideal rapid tests according to concept
malaria 16929 value of RDTs (from public health perspectives); therefore, the required specificity for effective malaria diagnosis is at least 97% or ideally 99% [[63]].Additional requirements for ideal RDTs are suitability
malaria 17079 [[63]].Additional requirements for ideal RDTs are suitability and appropriateness for LRS where most malaria cases occur. To make an impact simplicity and affordability are of utmost importance. Simplicity means,
malaria 17653 (2–40 °C) on reagent stability and usability of the devices [[67]].Microfluidic technology for malaria POC testingMicrofluidics enable the miniaturization and simplification of complicated analytical processes
malaria 20372 [79], [81], [86]–[94]].Table 5Performance of proof-of-concept platforms based on microfluidics for malaria detectionApplicationConcept/detection principleBiomarker/targetLimit of detectionPerformanceTime (min)RefsSensitivity
malaria 22130 mins[[94]]RBC red blood cell, iRBC infected red blood cellImmunodiagnostics on microfluidic platforms for malaria detectionStandard protocols to perform immunodiagnostics on microfabricated platforms require sample
malaria 22626 [96]]. Figure 3 presents some examples to illustrate how microfluidics technology can be used to detect malaria by different methods of detection, such as molecular testing, size-based cell sorting, electrical differentiation
malaria 22961 [[97]], (b) [[88]], (c) [[91]], (d) [[79]], (e) [[94]].Fig. 3Examples of microfluidic prototypes for malaria diagnosis using different methods. Reprinted with permission: a from [[86]], copyright 2016 Wiley–VCH,
malaria 23373 NatureSample pre-concentrationLow antigen concentration is a common problem in diagnostic immunoassays and malaria antigen detection is not an exception. To overcome this challenge, several prototypes of analyte concentrator
malaria 24853 separate cells successfully leading to promising prototypes for detecting infected red blood cells thus malaria infections [[101]–[103]].Flow controlControlling flow on microfabricated devices often introduces
malaria 26670 microfluidics systems also exist in the literature [[117]].Molecular testing on microfluidic platforms for malaria detectionAt the moment, PCR and LAMP are the most sensitive technique for identification of asymptomatic
malaria 34453 or gold nanoparticles [[141]–[143]]. At present, applications of smartphone-based diagnostics for malaria detection can be divided into two categories: phone-based RDT readers, which provides automatic interpretation
malaria 34997 external lenses and mirrorsMie scattering simulation onlineImmunoagglutination (Mie light scattering)PfHRP malaria biomarkerHuman bloodMicrobeads1 pg/mL–10 ng/mL[[144]]LOD 1 pg/mLComputational power + external
malaria 36736 readersA smartphone was used for quantitative reading of the Optimal-IT test, a commercially available malaria RDT with a snap-on unit as reader that is suitable for both Android and iPhone [[145]]. Images of RDTs
malaria 39214 diagnosis is the first step to further pursue efforts to eliminate and reduce the global burden of malaria by 90% in 2030. Current diagnostic methods can detect malaria symptomatic infections, but often miss
malaria 39276 eliminate and reduce the global burden of malaria by 90% in 2030. Current diagnostic methods can detect malaria symptomatic infections, but often miss out asymptomatic cases. The rise in proportion of asymptomatic
malaria 39639 advanced nowadays to (at least theoretically) be able to track down the last parasite carriers. While malaria case management has improved, other causes of fever need to be detected and treated accordingly. Therefore,
malaria 40082 phone-based readouts offer a unique opportunity to not only reduce the burden of infectious diseases, such as malaria , but also could provide tools for monitoring epidemics and elimination progress on very large scales
tuberculosis 290 date (pmc-release): 7/2018Publication date (collection): /2018AbstractMalaria, together with HIV/AIDS, tuberculosis and hepatitis are the four most deadly infectious diseases globally. Progress in eliminating malaria
tuberculosis 1380 malaria remains one of the four most life-threatening infectious diseases worldwide, together with tuberculosis , HIV/AIDS and hepatitis [[2]]. Latest data published by the World Health Organization (WHO) are staggering:

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