Lack of access to quality diagnostics remains a major contributor to health burden in resource-limited settings. It has been more than 10 years since ASSURED (affordable, sensitive, specific, user-friendly, rapid, equipment-free, delivered) was coined to describe the ideal test to meet the needs of the developing world. Since its initial publication, technological innovations have led to the development of diagnostics that address the ASSURED criteria, but challenges remain. From this perspective, we assess factors contributing to the success and failure of ASSURED diagnostics, lessons learnt in the implementation of ASSURED tests over the past decade, and highlight additional conditions that should be considered in addressing point-of-care needs. With rapid advances in digital technology and mobile health (m-health), future diagnostics should incorporate these elements to give us REASSURED diagnostic systems that can inform disease control strategies in real-time, strengthen the efficiency of health care systems and improve patient outcomes.
Subscribe to Journal
Get full journal access for 1 year
only $5.17 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Mabey, D., Peeling, R. W., Ustianowski, A. & Perkins, M. D. Diagnostics for the developing world. Nat. Rev. Microbiol. 2, 231–240 (2004).
Kettler, H., White, K. & Hawkes, S. Mapping the Landscape of Diagnostics for Sexually Transmitted Infections: Key Findings and Recommandations (UNICEF/UNDP/World Bank/WHO, 2004).
Sweeney, S. et al. The costs of accessible quality assured syphilis diagnostics: informing quality systems for rapid syphilis tests in a Tanzanian setting. Health Policy Plan. 29, 633–641 (2014).
HIV & Malaria Rapid Diagnostic Tests (Global Fund); https://www.theglobalfund.org/en/sourcing-management/health-products/hiv-malaria-rapid-diagnostic-tests/
Aledort, J. E. et al. Reducing the burden of sexually transmitted infections in resource-limited settings: the role of improved diagnostics. Nature 444, 59–72 (2006).
Gift, T. L., Pate, M. S., Hook, E. W. & Kassler, W. J. The rapid test paradox: when fewer cases detected lead to more cases treated: A decision analysis of tests for Chlamydia trachomatis. Sex. Transm. Dis. 26, 232–240 (1999).
Frost, L. & Reich, M. Access: How Do Good Health Technologies Get to Poor People in Poor Countries (Harvard Univ. Press, Cambridge, 2008).
Nkengasong, J. N., Yao, K. & Onyebujoh, P. Laboratory medicine in low-income and middle-income countries: progress and challenges. Lancet 391, 1873–1875 (2018).
Alemnji, G. A., Zeh, C., Yao, K. & Fonjungo, P. N. Strengthening national health laboratories in sub-Saharan Africa: a decade of remarkable progress. Trop. Med. Int. Heal. 19, 450–458 (2014).
Hay Burgess, D. C., Wasserman, J. & Dahl, C. A. Global health diagnostics. Nature 444, 1–2 (2006).
Urdea, M. et al. Requirements for high impact diagnostics in the developing world. Nature 444, 73–79 (2006).
Prequalification of In Vitro Diagnostics (WHO); http://www.who.int/diagnostics_laboratory/evaluations/en/
Pai, N. P., Tulsky, J. P., Cohan, D., Colford, J. M. & Reingold, A. L. Rapid point-of-care HIV testing in pregnant women: A systematic review and meta-analysis. Trop. Med. Int. Heal. 12, 162–173 (2007).
Consolidated Guidelines on HIV Testing Services (WHO, 2015).
Ghani, A. C., Burgess, D. H., Reynolds, A. & Rousseau, C. Expanding the role of diagnostic and prognostic tools for infectious diseases in resource-poor settings. Nature 528, 50–52 (2015).
Fonjungo, P. N. et al. Ensuring quality. AIDS 30, 1317–1323 (2016).
WHO-FIND Malaria RDT Evaluation Programme (WHO, 2017).
Poyer, S. et al. Availability and price of malaria rapid diagnostic tests in the public and private health sectors in 2011: Results from 10 nationally representative cross-sectional retail surveys. Trop. Med. Int. Heal. 20, 744–756 (2015).
Fact Sheet: World Malaria Report 2016 (WHO, 2016).
Cheng, Q. et al. Plasmodium falciparum parasites lacking histidine-rich protein 2 and 3: a review and recommendations for accurate reporting. Malar. J. 13, 283 (2014).
Rennie, W. et al. Minimising human error in malaria rapid diagnosis: clarity of written instructions and health worker performance. Trans. R. Soc. Trop. Med. Hyg. 101, 9–18 (2007).
Harvey, S. A. et al. Improving community health worker use of malaria rapid diagnostic tests in Zambia: package instructions, job aid and job aid-plus-training. Malar. J. 7, 160 (2008).
Peeling, R. W. et al. Syphilis. Nat. Rev. Dis. Prim. 3, 17073 (2017).
The Global Elimination of Congenital Syphilis: Rationale and Strategy for Action (WHO, Department of Reproductive Health and Research, 2007).
Gomez, G. B. et al. Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis. Bull. World Health Organ. 91, 217–226 (2013).
Newman, L. et al. Global estimates of syphilis in pregnancy and associated adverse outcomes: analysis of multinational antenatal surveillance data. PLoS Med. https://doi.org/10.1371/journal.pmed.1001396 (2013).
Tucker, J. D. et al. Accelerating worldwide syphilis screening through rapid testing: a systematic review. Lancet Infect. Dis. 10, 381–386 (2018).
Jafari, Y. et al. Are Treponema pallidum specific rapid and point-of-care tests for syphilis accurate enough for screening in resource limited settings? Evidence from a meta-analysis. PLoS ONE 8, e54695 (2013).
Swartzendruber, A., Steiner, R. J., Adler, M. R., Kamb, M. L. & Newman, L. M. Introduction of rapid syphilis testing in antenatal care: a systematic review of the impact on HIV and syphilis testing uptake and coverage. Int. J. Gynecol. Obstet. 130, 15–21 (2015).
Shelley, K. D. et al. Scaling down to scale up: a health economic analysis of integrating point-of-care syphilis testing into antenatal care in Zambia during pilot and national rollout implementation. PLoS ONE 10, e0125675 (2015).
Ansbro, É. M. et al. Introduction of syphilis point-of-care tests, from pilot study to national programme implementation in Zambia: a qualitative study of healthcare workers’ perspectives on testing, training and quality assurance. PLoS ONE 10, e0127728 (2015).
Peeling, R. W., Mabey, D., Fitzgerald, D. W. & Watson-Jones, D. Avoiding HIV and dying of syphilis. Lancet 364, 1561–1563 (2004).
Taylor, M. et al. Elimination of mother-to-child transmission of HIV and Syphilis (EMTCT): process, progress, and program integration. PLoS Med. 14, e1002329 (2017).
Wijesooriya, N. S. et al. Global burden of maternal and congenital syphilis in 2008 and 2012: a health systems modelling study. Lancet Glob. Health 4, e525–e533 (2016).
Peeling, R. W. & Mabey, D. Celebrating the decline in syphilis in pregnancy: a sobering reminder of what’s left to do. Lancet Glob. Health 4, e503–e504 (2016).
Gliddon, H. D. et al. A systematic review and meta-analysis of studies evaluating the performance and operational characteristics of dual point-of-care tests for HIV and syphilis. Sex. Transm. Infect. 93, S3–S15 (2017).
WHO Guideline on Syphilis Screening and Treatment for Pregnant Women (WHO, 2017).
Sustainable Development Goals (UN); https://sustainabledevelopment.un.org/?menu=1300
Lawn, S. D., Kerkhoff, A. D., Vogt, M. & Wood, R. Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: a descriptive study. Lancet Infect. Dis. 12, 201–209 (2012).
Fact Sheets on Tuberculosis (WHO); https://www.who.int/tb/publications/factsheets/en/
Pathmanathan, I. et al. Rolling out Xpert MTB/RIF® for tuberculosis detection in HIV-positive populations: An opportunity for systems strengthening. Afr. J. Lab. Med. 6, 460 (2017).
Lawn, S. D. et al. Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future prospects for a point-of-care test. Lancet Infect. Dis. 13, 349–361 (2013).
Schito, M. et al. Perspectives on advances in tuberculosis diagnostics, drugs, and vaccines. Clin. Infect. Dis. 61, S102–S118 (2015).
Hermans, S., Caldwell, J., Kaplan, R., Cobelens, F. & Wood, R. The impact of the roll-out of rapid molecular diagnostic testing for tuberculosis on empirical treatment in Cape Town, South Africa. Bull. World Health Organ. 95, 554–563 (2017).
WHO End TB Strategy (WHO); http://www.who.int/tb/post2015_strategy/en/
Abubakar, I. et al. Drug-resistant tuberculosis: time for visionary political leadership. Lancet Infect. Dis. 13, 529–539 (2013).
Clouse, K. et al. Implementation of Xpert MTB/RIF for routine point-of-care diagnosis of tuberculosis at the primary care level. South African Med. J. 102, 805–807 (2012).
Peeling, R. W. et al. Evaluation of diagnostic tests: dengue. Nat. Rev. Microbiol. 8, S30–S38 (2010).
Goncalves, A. et al. Innovative and new approaches to laboratory diagnosis of Zika and Dengue: a meeting report. J. Infect. Dis. 217, 1060–1068 (2018).
Chappuis, F. et al. Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat. Rev. Microbiol. 5, 873–882 (2007).
Marks, M. et al. Metaanalysis of the performance of a combined treponemal and nontreponemal rapid diagnostic test for syphilis and yaws. Clin. Infect. Dis. 63, 627–633 (2016).
Kelly, H. et al. Systematic reviews of point-of-care tests for the diagnosis of urogenital Chlamydia trachomatis infections. Sex. Transm. Infect. 93, S22–S30 (2017).
Guy, R. J. et al. Performance and operational characteristics of point-of-care tests for the diagnosis of urogenital gonococcal infections. Sex. Transm. Infect. 93, S16–S21 (2017).
Gift, T. L., Pate, M. S., Hook III, E. W. & Kassler, W. J. The rapid test paradox: when fewer cases detected lead to more cases treated: a decision analysis of tests for Chlamydia trachomatis Sex. Transm. Dis. 26, 232–240 (1999).
Meggi, B. et al. Point-of-care p24 infant testing for HIV may increase patient identification despite low sensitivity. PLoS ONE 12, e0169497 (2017).
Peeling, R. W. & McNerney, R. Emerging technologies in point-of-care molecular diagnostics for resource-limited settings. Expert Rev. Mol. Diagn. 14, 525–534 (2014).
LaBarre, P. et al. A simple, inexpensive device for nucleic acid amplification without electricity-toward instrument-free molecular diagnostics in low-resource settings. PLoS ONE 6, e19738 (2011).
Bissonnette, L. & Bergeron, M. G. Expert review of molecular diagnostics portable devices and mobile instruments for infectious diseases point-of-care testing. Expert Rev. Mol. Diagn. 17, 471–494 (2017).
Laksanasopin, T. et al. A smartphone dongle for diagnosis of infectious diseases at the point of care. Sci. Transl. Med. 7, 273re1 (2015).
Sharma, S., Zapatero-Rodríguez, J., Estrela, P. & O’Kennedy, R. Point-of-care diagnostics in low resource settings: present status and future role of microfluidics. Biosensors 5, 577–601 (2015).
Sackmann, E. K., Fulton, A. L. & Beebe, D. J. The present and future role of microfluidics in biomedical research. Nature 507, 181–189 (2014).
Yang, K., Peretz-Soroka, H., Liu, Y. & Lin, F. Novel developments in mobile sensing based on the integration of microfluidic devices and smartphones. Lab Chip 16, 943–958 (2016).
Roda, A. et al. Integrating biochemiluminescence detection on smartphones: mobile chemistry platform for point-of-need analysis. Anal. Chem. 86, 7299–7304 (2014).
O’Farrell, B. Lateral flow technology for field-based applications—basics and advanced developments. Top. Companion Anim. Med. 30, 139–147 (2015).
Wedderburn, C. J., Murtagh, M., Toskin, I. & Peeling, R. W. Using electronic readers to monitor progress toward elimination of mother-to-child transmission of HIV and syphilis: an opinion piece. Int. J. Gynecol. Obstet. 130, S81–S83 (2015).
Fitzpatrick, C. & Engels, D. Leaving no one behind: a neglected tropical disease indicator and tracers for the Sustainable Development Goals. Int. Health 8, i15–i18 (2015).
Smit, P. W. et al. The trade-off between accuracy and accessibility of syphilis screening assays. PLoS ONE 8, e75327 (2013).
Bell, D., Wongsrichanalai, C. & Barnwell, J. W. Ensuring quality and access for malaria diagnosis: how can it be achieved? Nat. Rev. Microbiol. 4, 682–695 (2006).
Nkengsong, J., Boeras, D. I., Abimiku, A. & Peeling, R. W. Assuring the quality of diagnostic testing: the future is now. Afr. J. Lab. Med. 5, 4–5 (2016).
Boeras, D. I. & Peeling, R. W. External quality assurance for HIV point-of-care testing in Africa: a collaborative country-partner approach to strengthen diagnostic services. Afr. J. Lab. Med. 5, 2 (2016).
Boeras, D. I., Nkengasong, J. N. & Peeling, R. W. Implementation science: the laboratory as a command centre. Curr. Opin. HIV AIDS 12, 171–174 (2017).
Vassall, A. et al. Cost-effectiveness of Xpert MTB/RIF for tuberculosis diagnosis in South Africa: a real-world cost analysis and economic evaluation. Lancet Glob. Heal. 5, e710–e719 (2017).
Churchyard, G. J. et al. Xpert MTB/RIF versus sputum microscopy as the initial diagnostic test for tuberculosis: a cluster-randomised trial embedded in South African roll-out of Xpert MTB/RIF. Lancet Glob. Heal. 3, e450–e457 (2015).
Mabey, D. C. et al. Point-of-care tests to strengthen health systems and save newborn lives: the case of syphilis. PLoS Med. 9, 8 (2012).
García, P. J. et al. Rapid syphilis tests as catalysts for health systems strengthening: a case study from Peru. PLoS ONE 8, e66905 (2013).
St John, A. & Price, C. P. Existing and emerging technologies for point-of-care testing. Clin. Biochem. Rev. 35, 155–167 (2014).
O’Neill, J. Tackling Drug-Resistant Infections Globally: Final Report and Recommendations (AMR Review, 2016).
Gous, N. et al. Expert review of molecular diagnostics: the impact of digital technologies on point-of-care diagnostics in resource-limited settings. Expert Rev. Mol. Diagn. 18, 385–397 (2018).
Denkinger, C. M., Grenier, J., Stratis, A. K., Akkihal, A. & Pai, M. Mobile health to improve tuberculosis care and control: a call worth making. 17, 719–727 (2013).
Wood, C. et al. Bringing mHealth connected infectious disease diagnostics to the field. Nature (in the press).
Hamedi, M. M. et al. Integrating electronics and microfluidics on paper. Adv. Mater. 28, 5054–5063 (2016).
Morgan, H. et al. From Smartphones to Diagnostics : Low Cost Electronics for Programmable Digital Microfluidics and Sensing (Univ. Southampton, 2015).
Liang, T., Zou, X. & Mazzeo, A. D. A flexible future for paper-based electronics. Proc. SPIE https://doi.org/10.1117/12.2224391 (2016).
Turner, A. P. F. Biosensors: sense and sensibility. Chem. Soc. Rev. 42, 3184 (2013).
Chen, X. S. Rapid diagnostic tests for neurosyphilis. Lancet Infect. Dis. 13, 918–919 (2013).
Engel, N. et al. Compounding diagnostic delays: a qualitative study of point-of-care testing in South Africa. Trop. Med. Int. Heal. 20, 493–500 (2015).
Cheng, B. et al. Data connectivity: a critical tool for external quality assessment. Afr. J. Lab. Med. 5, 535 (2016).
Smith, S., Oberholzer, A., Land, K., Korvink, J. G. & Mager, D. Functional screen printed radio frequency identification tags on flexible substrates, facilitating low-cost and integrated point-of-care diagnostics. Flex. Print. Electron. 3, 025002 (2018).
Govindarajan, A. V., Ramachandran, S., Vigil, G. D., Yager, P. & Böhringer, K. F. A low cost point-of-care viscous sample preparation device for molecular diagnosis in the developing world; an example of microfluidic origami. Lab Chip 12, 174–181 (2012).
Nery, E. W. & Kubota, L. T. Sensing approaches on paper-based devices: a review. Anal. Bioanal. Chem. 405, 7573–7595 (2013).
Martinez, A. W., Phillips, S. T., Whitesides, G. M. & Carrilho, E. Diagnostics for the developing world: microfluidic paper-based analytical devices. Anal. Chem. 82, 3–10 (2010).
Cate, D. M., Adkins, J. A., Mettakoonpitak, J. & Henry, C. S. Recent developments in paper-based microfluidic devices. Anal. Chem. 87, 19–41 (2015).
Pardee, K. et al. Paper-based synthetic gene networks. Cell 159, 940–954 (2014).
X.-S.C. receives research funding from the Chinese Academy Medical Sciences Initiative for Innovative Medicine (2016-I2M-3-021). K.J.L. receives CSIR parliamentary grant funding. R.W.P. receives funding from the UK Engineering and Physical Sciences Research Council (EPSRC) i-sense Early Warning Sensing Systems in Infectious Disease (EP/K031953/1).
The authors declare no competing interests.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Land, K.J., Boeras, D.I., Chen, X. et al. REASSURED diagnostics to inform disease control strategies, strengthen health systems and improve patient outcomes. Nat Microbiol 4, 46–54 (2019) doi:10.1038/s41564-018-0295-3
Nanomaterials for molecular signal amplification in electrochemical nucleic acid biosensing: recent advances and future prospects for point-of-care diagnostics
Molecular Systems Design & Engineering (2020)
Microchimica Acta (2019)
Frontiers in Medicine (2019)
Accounts of Chemical Research (2019)
Lab on a Chip (2019)